Professor Dulcie Mulholland

The structure of ferrugin (1) from Aglaia ferruginaea has been revised to be the same as rocaglaol (2) which has been isolated from Aglaia odorata. The structure of ferrugin from Aglaia ferruginaea has been revised to be the same as rocaglaol which has been isolated from Aglaia odorata.

A methylene chloride extract of Mondia whitei (Hook.f.) Skeels yielded 2-hydroxy-4-methoxybenzaldehyde and 3-hydroxy-4-methoxybenzatdehyde (isovanillin). Chemical structures of the constituents were determined by comparing 1H NMR spectra to that of known compounds. Although the 2-hydroxy-4-methoxybenzaldehyde had been isolated previously from Mondia whitei, isovanillin had not been observed in the plant.

Brunsvigia radulosa Herb. is a bulbous ethnomedicinal herb, widespread from the Great Karoo northwards through the grasslands of southern Africa. Earlier workers have previously identified a total of ten isoquinoline alkaloids from this taxon, including 1-O-acetylnorpluviine which is only known from B. radulosa. The current report investigates the suggestions of earlier workers relating to the psychoactivity of the bulb constituents, and its usefulness in the traditional treatment of cancer. The identification of anhydrolycorinium chloride, the second ever isolation of this compound from a plant, supports earlier observations for antineoplastic activity of bulb and leaf extracts of B. radulosa in a mouse P-388 lymphocytic leukaemia system. In the current study, 1-O-acetyllcorine was also isolated from the bulbs.

Cassipourea congoensis (syn. Cassipourea malosana) is used in African countries as a skin-lightening agent. Two previously unreported cycloartane triterpenoids, 26-hydroxy-3-keto-24-methy lenecycloartan-30-oic acid 1 and 24-methylene-cycloartan-3β,26,30-triol 2 along with the known mahuannin B 3, 7-methoxymahuannin B 4, 7-methoxygeranin A 5, methyl-3-(4-hydroxy-3-methoxyphenyl)-2E-propenoate, glycerol-1-alkanoate, (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enal 6, (-)-syringaresinol 7, and stigmast-5-en-3-O-β-D-glucoside, were isolated from the roots of C. congoensis. The crude extract and compounds 1 and 5 were found to inhibit the production of melanin at 10 μM with low cytotoxicity validating the ethno-medicinal use of this plant

A phytochemical investigation of the roots of Citrus x paradisi Macfad. (Rutaceae) led to the isolation of two new compounds, namely 1-formyl-5-hydroxy-N-methylindolin-1-ium (1) and decyloxycleomiscosin D (2), along with ten known compounds: 1,1-dimethylpyrrolidin-1-ium-2-carboxylate (3), furan-2,3-diol (4), 5-methoxyseselin (5), umbelliferone (6), scopoletin (7), citracridone I (8), citracridone II (9), citracridone III (10), limonin (11) and lupeol (12). The structures were determined through the comprehensive spectroscopic analysis of 1D and 2D NMR and EI- and ESI-MS, as well as a comparison with the published data. Notably, compounds 3 and 4 from the genus Citrus are reported here for the first time. In addition, the MeOH extract of the roots and compounds 1-7 were screened against the human adenocarcinoma alveolar basal epithelial cell line A549 and the Caucasian prostate adenocarcinoma cell line PC3 using the MTT assay. While the extract showed significant activity, with IC50 values of 35.2 and 38.1 mu g/mL, respectively, compounds 1-7 showed weak activity, with IC50 values of 99.2 to 250.2 mu M and 99.5 to 192.7 mu M, respectively.

A novel flavonoid, (-)-2R,3R-3,5,4′-trihydoxyflavan-[6,7:5″, 6″]-2″-pyranone, named uncariechin (1), was isolated from the methanolic extract of the leaves of Uncaria longiflora var. pteropoda (Miq.) Ridsd. along with the known (-)-epiafzelechin (2) and (-)-epicatechin (3), methyl 4-hydroxybenzoate and 4-hydroxybenzaldehyde, four pentacyclic oxindole alkaloids, isopteropodine, pteropodine, uncarine F and isopteropodic acid, previously found in the stems, and two coumarins, scopoletin and 3,4-dihydroxy-7-methoxycoumarin. Structures of the compounds were elucidated by 1D and 2D NMR, FTIR, UV, MS, and experimental as well as calculated electronic circular dichroism (ECD) data. Compounds 2 and 3 were evaluated for their neurotoxic and neuroprotective properties against differentiated SH-SY5Y neuroblastoma cell lines using the MTS assay. Compounds 2 and 3 did not show any neurotoxic effects but showed strong protective potential against hydrogen peroxide-induced neurotoxicity with maximum cell viability at a concentration of 1 μM. © 2013 Phytochemical Society of Europe.

Langaside (1), a secoiridoid lactone glucoside possessing a novel skeleton formed by a [2 + 2] cycloaddition reaction between the secoiridolactone glucoside, 1,9-trans-9,5-cis-sweroside, and p-coumaric acid was isolated from the fruits and flowers of the Malagasy Tachiadenus longiflorus Griseb. (Gentianaceae), alongside another seven known compounds. The structure of langaside was established using HRESIMS, IR and NMR spectroscopy and comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Langaside was screened for its neuritogenic activity against SHSY-5Y cells and anticancer activity against the NCI59 human tumour cell panel but not found to be active.

Excessive blood vessel formation in the eye is implicated in wet age-related macular degeneration, proliferative diabetic retinopathy, neovascular glaucoma, and retinopathy of prematurity, which are major causes of blindness. Small molecule antiangiogenic drugs are strongly needed to supplement existing biologics. Homoisoflavonoids have been previously shown to have potent antiproliferative activities in endothelial cells over other cell types. Moreover, they demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Here, we tested the antiangiogenic activity of a group of naturally occurring homoisoflavonoids isolated from the family Hyacinthaceae and related synthetic compounds, chosen for synthesis based on structure–activity relationship observations. Several compounds showed interesting antiproliferative and antiangiogenic activities in vitro on retinal microvascular endothelial cells, a disease-relevant cell type, with the synthetic chromane, 46, showing the best activity (GI50 of 2.3 × 10–4 μM).

The fruits of Kigelia africana (Lam.) Benth. are a popular source of traditional medicine throughout Africa. The stembark has been widely analysed for pharmacological activity, yet knowledge of the fruits is limited, despite more extensive use in traditional remedies. Crude extracts of stembark and fruits were prepared with distilled water, ethanol or ethyl acetate. In the microtitre plate bioassay, stembark and fruit extracts showed similar antibacterial activity against Gram-negative and Gram-positive bacteria. A mixture of three fatty acids exhibiting antibacterial effects was isolated from the ethyl acetate extract of the fruits using bioassay-guided fractionation. Palmitic acid, already known to possess antibacterial activity, was the major compound in this mixture. These results confirm antibacterial activity of K. africana fruits and stembark, and support the traditional use of the plant in therapy of bacterial infections.

Extraction of the whole plant of Turraea obtusifolia has given prieurianin, a complex limonoid of known structure which is a useful taxonomic marker. Extraction of Turraea floribunda gave a mixutre of limonoids, apparently of the same group as prieurianin but of a lower oxidation state. Three of these have been isolated and the structure determined, mainly by spectroscopic methods.

Two novel protolimonoids, 7-deacetylglabretal-3-acetate and 7-deacetylglabretal-3-tiglate were isolated from the powdered heartwood of Algaia ferruginaea. 7-Deacetylglabretal-3-acetate was isolated from the wood of Turraea obtusifolia.

The stem bark of Astrotrichilia voamatata (Meliaceae) yielded the novel limonoids voamatin A and voamatin B. The stem bark of Cipadessa boivinina (Meliaceae) yielded sitosterol and stigmast-4-en-3-one, but no limonoids.

Covering: 1914 to 2012The Hyacinthaceae (sensu APGII), with approximately 900 species in about 70 genera, can be divided into three main subfamilies, the Hyacinthoideae, the Urgineoideae and the Ornithogaloideae, with a small fourth subfamily the Oziroëoideae, restricted to South America. The plants included in this family have long been used in traditional medicine for a wide range of medicinal applications. This, together with some significant toxicity to livestock has led to the chemical composition of many of the species being investigated. The compounds found are, for the most part, subfamily-restricted, with homoisoflavanones and spirocyclic nortriterpenoids characterising the Hyacinthoideae, bufadienolides characterising the Urgineoideae, and cardenolides and steroidal glycosides characterising the Ornithogaloideae. The phytochemical profiles of 38 genera of the Hyacinthaceae will be discussed as well as any biological activity associated with both crude extracts and compounds isolated. The Hyacinthaceae of southern Africa were last reviewed in 2000 (T. S. Pohl, N. R. Crouch and D. A. Mulholland, Curr. Org. Chem., 2000, 4, 1287-1324; ); the current contribution considers the family at a global level.

BACKGROUND: Plant extracts might provide sustainable alternatives to copper fungicides, which are still widely used despite their unfavourable ecotoxicological profile. Larch bark extract and its constituents, larixyl acetate and larixol, have been shown to be effective against grapevine downy mildew (Plasmopara viticola) under semi-controlled conditions. The aim of this study was to reduce the gap between innovation and the registration of a marketable product, namely to develop scalable extraction processes and to evaluate and optimize performance of larch extracts under different conditions. RESULTS: Toxicologically and technically acceptable solvents like ethanol were used to extract the active compounds larixyl acetate and larixol from bark in sufficient amounts and their combined concentration could be increased up to 39% by purification steps. The combined concentration of larixyl acetate and larixol from larch turpentine could be increased up to 66%. MIC100 against P. viticola in vitro (6-23 g mL-1) and EC50 in planta under semi-controlled conditions (0.2-0.4 mg mL-1) were promising compared to other plant extracts. In vineyards, efficacies of larch extracts reached up to 68% in a stand-alone strategy and 84% in low-copper strategies. CONCLUSIONS: Larch extracts represent valid candidates for copper reduction in organic vineyards, and their development into a sustainable plant protection product might be feasible

Pumilol (1), a strobane diterpenoid, reported herein for the first time was isolated from the bark of Pinus pumila (Pall.) Regel (Siberian Dwarf Pine or Japanese Stone Pine), along with seventeen known compounds including serratane triterpenoids, not previously reported from this species, and four ferulate derivatives. The stereostructure of pumilol was established using HRESIMS, NMR, the DP4+ probabilities and by comparison of the experimental and calculated electronic circular dichroim (ECD) spectra. Labda-8(17),13-dien-15-oic acid (4), bornyl trans-4-hydroxycinnamate (14) and E-bornyl ferulate (15) showed activity against S. aureus and/or E. faecalis with MIC90 values 12.5-50 µM.

Antibacterial bioassay-guided fractionation of an ethyl acetate root extract of Terminalia sericea led to the isolation of anolignan B. The isolated compound was further tested for anti-inflammatory activity using the cyclooxygenase enzyme assays (COX-1 and COX-2) and for potential mutagenic effects using the Ames test. In the antibacterial test, anolignan B showed activity against both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration values obtained (MIC) ranged from 3.8 microg/ml against Bacillus subtilis (Gram-positive) to 31 microg/ml against Escherichia coli (Gram-negative). In the anti-inflammatory assays, anolignan B showed activity against both COX-1 (IC(50) = 1.5 mM) and COX-2 (IC(50) = 7.5 mM) enzymes. No potential mutagenic effects were observed in the Salmonella microsome assay (TA98). Isolation of anolignan B from Terminalia sericea as well as the antibacterial and anti-inflammatory activities observed in this study has not been reported previously.

Fourteen compounds were isolated from the roots, leaves and twigs of Penianthus longifolius Miers (Menispermaceae), including two previously unreported neo-clerodane diterpenoids, penianthin (1), its C-8 epimer (2). In addition, the previously reported O-methylmoschatoline (3), taraxerol (4), taraxerone (5), rubrosterone, (6), panuosterone (7), 22-epi-20-hydroxyecdysone (8), ergosterol peroxide (9), stigmast-5-ene-3,7-dione (10), stigmasterol (11), β-sitosterol (12), stigmasterol glucoside (13) and β-sitosterol glucoside (14) were isolated. The structures of the compounds were determined by means of NMR spectroscopic and mass spectrometric analysis. The absolute configurations of 1 and 2 were determined by circular dichroism analysis. Compounds 1 and 2 were screened against the NCI60 cancer cell panel but showed no significant activity at 10 μM.

A phytochemical investigation of the stem barks of the Malaysian Croton oblongus Burm.f. (Syn. Croton laevifolius Blume) (Euphorbiaceae) yielded seven previously undescribed ent-neo-clerodane diterpenoids, laevifins A - G (1, 2, 4-8) and the known crovatin (3). Structures were established by a combination of spectroscopic methods including HRESIMS, NMR spectroscopy and X-ray crystallography. The absolute configuration of crovatin and laevifins A-G was established by comparison of experimental ECD and theoretical TDDFT ECD calculated spectra. This is the first report on the occurrence of the sesquiterpenoid cryptomeridiol in a Croton species. In vitro cytotoxicity assays on laevifins A (1), B (2) and G (8) showed moderate activities against the MCF-7 cancer cell line (IC50 102, 115 and 106 μM, respectively) while β-amyrin and acetyl aleuritolic acid showed good anti-inflammatory activity on the LPS-induced NF-κB translocation inhibition in RAW 264.7 cells assay with IC50 values of 23.5 and 35.4 μg/mL, respectively.

The antibacterial activity of the ethanolic root extract of Cassia occidentalis was examined. A biologically active component was isolated and identified as emodin by spectroscopic analysis. The bioactive Minimum Inhibitory Concentration (MIC) values of emodin were 7.8 × 10- 3 and 3.9 × 10- 3 mg ml- 1 against Bacillus subtilis and Staphylococcus aureus, respectively. It was not active against two Gram-negative bacteria (Klebsiella pneumoniae and Escherichia coli) at the highest concentration (5.0 × 10- 1 mg ml- 1) tested. © 2005 Elsevier B.V. All rights reserved.

Toddaliopsins A-D, four novel 1,2,3-trioxygenated acridone alkaloids, have been isolated from the leaves of Toddaliopsis bremekampii. Toddaliopsins B-D are the first reported acridone alkaloids with substituted N-methyl groups, in the light of which the chemotaxonomic relationship of Toddaliopsis and Vepris is discussed. Toddaliopsin C possesses moderate anti-inflammatory activity, which may be related to the hydroxy group present at C-1.

We investigated the antimicrobial activity of heat‐treated woodchips of three woody host species against the invasive oomycete plant pathogen Phytophthora ramorum to assess the potential of heated woodchips for disease suppression. Results demonstrated that heat‐treated pine (Pinus sylvestris), Japanese larch (Larix kaempferi) and rhododendron (Rhododendron ponticum) woodchips inhibited the recovery of P. ramorum spores and mycelium compared with similar material that had only been air‐dried. Effects were most evident with pine and larch; inhibition was maintained even when larch woodchips were diluted with soil. In vitro assays using methanol crude extracts from woodchips of the three species showed they all had an inhibitory effect on P. ramorum zoospores and reduced chlamydospore germination compared with air‐dried wood extracts. Chemical analysis of the extracts revealed several induced compounds were present but in different concentrations for each species. Coniferaldehyde was the most active inhibitory against spores and mycelium, whilst the dominant resin acids, dehydroabietic and abietic acid, decreased the minimum inhibitory concentration of phenolic compounds tested against P. ramorum but were ineffective when used alone. An array of compounds, including dehydroabietic acid, methyl abietate, α‐pinene and 3‐carene, occurred at elevated levels in the living tissue of Japanese larch bark attacked by P. ramorum. These compounds may be part of the induced resistance response of larch to P. ramorum. Results of a field trial using heat‐treated and air‐dried woodchips were consistent with the crude extract bioassay results, suggesting that heat‐treated woody materials have potential to reduce the survival of P. ramorum under natural conditions.

The bulbs of Eucomis bicolor (Hyacinthoideae) yielded fourteen novel natural compounds, including (17S)-3-oxo-24,25,26,27,28-pentanorlanost-8-en-23,17α-olide, whose structure was determined using the Logic for Structure Determination Program, and nine novel lanosterol glycosides. Compounds were screened against the NCI-59 cancer cell panel but showed limited activity.

The synthesis of the pyranonaphthoquinone antibiotic pentalongin was performed using the phthalide annulation strategy. Annulation of the cyanophthalide onto 6H-pyran-3-one resulted in a hongconin analogue, which upon further elaboration was converted into the natural product. © Georg Thieme Verlag Stuttgart.

We report on the first phytochemical investigation of a member of the African genus Resnova (Hyacinthoideae: Hyacinthaceae). From the dichloromethane extract of the bulbs of both Resnova humifusa and Eucomis montana (Hyacinthoideae: Hyacinthaceae) a novel 3-benzyl-4-chromanone homoisoflavonoid, 5,6-dimethoxy-7-hydroxy-3-(4′-hydroxybenzyl)-4-chromanone, was isolated. A further 11 known homoisoflavonoids were also identified, the 12 in total presenting a clear biosynthetic sequence. Eight of the 12 compounds found were common to both species. © 2005 Elsevier Ltd. All rights reserved.

The traditional use of medicinal plants in southern Africa is widespread with over 80% of South African households using medicinal plants. A mushrooming of research into the study of medicinal plants in the developing world has occurred but most of Africa is lagging behind in research output despite long traditions of medicinal plant usage. A considerable investment in research infrastructure is required.

Dichloromethane and 90% methanol extracts of 42 South African plants were screened for mutagenicity and antimutagenicity using the Salmonella/microsome mutagenicity assay (Ames) against Salmonella typhimurium TA98 and TA100 bacterial strains in the presence and absence of metabolic activator S9. The methanol extracts from whole plants of Helichrysum simillimum, Helichrysum herbaceum and Helichrysum rugulosum indicated mutagenicity. These are the first reported tests on the mutagenicity of Helichrysum species. Six species indicated antimutagenic properties, all in the presence of S9: methanol leaf extract of Bauhinia galpinii, and dichloromethane leaf extracts of Bauhinia galpinii, Clerodendrum myricoides, Datura stramonium, Buddleja saligna, Millettia sutherlandii and Sutherlandia frutescens.

Bioactivity-guided fractionation of the petroleum ether extract of the leaves of Hyptis suaveolens, widely used in Traditional Medicine, has led to the isolation of an abietane-type diterpenoid endoperoxide, 13 alpha-epi-dioxiabiet-8(14)-en-18-ol, displaying high antiplasmodial activity (IC(50) 0.1 microg/ml).

Five ergostanes, dimethylincisterol (1), 5α,8α–epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol (2), 5α,8α–epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol (3), 5α,6α-epoxy-(22E,24R)-ergosta-8(14),22-diene-3β,7α-diol (4), (22E,24R)-ergosta-7,22-diene-3β,5α,6β-triol (5) and betulinic acid (6) were isolated from the fresh fruiting bodies of the edible mushroom, Termitomyces microcarpus. The cytotoxicity of the compounds isolated was evaluated against the NCI 60 human cancer cell line panel. The degraded sterol dimethylincisterol (1) and 5α,8α–epidioxyergosta-6,22-dien-3β-ol (3) possessed cytotoxic activity at the 1 µM level.

Two new acridone alkaloids, verdoocridone A (1) and B (4), together with fifteen known compounds were isolated from methanol extracts of the roots and leaves of Vepris verdoorniana. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR, EI- and ESI– MS). The 13C NMR values of 1,2,3,5-tetramethoxy-N-methylacridone (2) and 5-methoxyaborinine (3) are also reported. The crude extracts and compounds (1-6) were tested for their antimicrobial activity. The test delivered moderate activities for crude extracts and compounds 1, 5 and 6 against the bacterium Staphylococcus aureus and the fungi Mucor meihei and Candida albicans with MIC values between 115 and 180mg/mL for extracts and between 21.3 and 29.4mM for compounds, compared to gentamycin with 0.2mM and nystatin with 5.2mM against both fungi. The determination of the radical scanvenging activity using 1,1-dephenyl-2-picrylhydrazyl (DPPH) assay gave moderate antioxidant values for all tested compounds, with IC50 between 0.29 and 0.41mM, compared to the standard 3-t-butyl-4- hydroxyanisole (BHA) displaying 0.03mM.

Two new 5,10b-ethanophenanthridine bridge alkaloids, 3-O-methyl–epi–vittatine, 1, and crouchinine, 2, (2R)-7-hydroxyflavan, 3, and a novel ceramide, brunsceramide, were isolated from the bulbs of Brunsvigia natalensis. (2R)-7-Hydroxyflavan showed total growth inhibition in the 55–60 ppm range against the melanoma (UACC62), breast (MCF7) and renal (TK10) cancer cell lines. 3-O-Methyl–epi–vittatine, 1, and bruns-ceramide, 4, were inactive against the cell lines tested.

The leaf extract of Croton haumanianus J. Léonard (Euphorbiaceae) yielded twenty-six compounds, including eight previously reported ent-kauranes and an ent-labdane and eight undescribed ent-kauranes, ent-16R-kauran-17-al, ent-3β-hydroxy-16R-kauran-17-al, ent-16S,17-epoxykauran-19-ol, ent-16S,17-epoxykauran-3β-ol, ent-17-palmityloxykaurane-3β,16β-diol, ent-17-palmityloxykauran-16β-ol, ent-3α,18-cyclokaurane-16β,17-diol and 19-nor-16α,17-dihydroxy-ent-kaur-4(18)-ene and three undescribed ent-clerodanes, dimethyl ent-15,16-epoxy-6β-hydroxy-1,3,13(16),14-clerodatetraen-20,12S-olide-18,19-dioate (saniolide A), dimethyl ent-15,16-epoxy-6β-hydroxy-1,3,13(16),14-clerodatetraen-20,12R-olide-18,19-dioate (12-epi-saniolide A), methyl ent-15,16-epoxy-1,3,13(16),14-clerodatetraen-18,6R:20,12S-diolide-19-oate (saniolide B) . The stem bark extract yielded the ent-clerodane crotocorylifuran, and five undescribed ent-isopimaranesent-isopimara-8(14),15-dien-18-al, ent-18-hydroxyisopimara-8(14),15-dien-7-one, ent-isopimara-7,15-dien-18-oic acid, ent-isopimara-7,15-dien-18-ol and ent-isopimara-8,15-dien-7-oxo-18-oic acid. Three compounds, ent-kaurane-3β,16β,17-triol, ent-17-palmityloxykaurane-3β,16β-diol and ent-17-palmityloxykauran-16β-ol, showed selective activity against three of the NCI 60 cancer cell lines, the colon (HCT-116), the melanoma (M14) and the renal (786-0) cancer cell lines at a concentration of 10-5 M.

Background Homoisoflavonoids have been shown to have potent anti-proliferative activities in endothelial cells over other cell types and have demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Three species of Rhodocodon (Scilloideaea subfamily of the Asparagaceae family), endemic to Madagascar, R. cryptopodus, R. rotundus and R. cyathiformis, were investigated. Purpose To isolate and test homoisoflavonoids for their antiangiogenic activity against human retinal microvascular endothelial cells (HRECs), as well as specificity against other ocular cell lines. Methods Plant material was extracted at room temperature with EtOH. Compounds were isolated using flash column chromatography and were identified using NMR and CD spectroscopy and HRESIMS. Compounds were tested for antiproliferative effects on primary human microvascular retinal endothelial cells (HRECs), ARPE19 retinal pigment epithelial cells, 92–1 uveal melanoma cells, and Y79 retinoblastoma cells. HRECs exposed to compounds were also tested for migration and tube formation ability. Results Two homoisoflavonoids, 3S-5,7-dihydroxy-(3′-hydroxy-4′-methoxybenzyl)-4-chromanone (1) and 3S-5,7-dihydroxy-(4′-hydroxy-3′-methoxybenzyl)-4-chromanone (2), were isolated along with four bufadienolides. Compound 1 was found to be non-specifically antiproliferative, with GI50 values ranging from 0.21–0.85 μM across the four cell types, while compound 2 showed at least 100-fold specificity for HRECs over the other tested cell lines. Compound 1, with a 3S configuration, was 700 times more potent that the corresponding 3R enantiomer recently isolated from a Massonia species. Conclusion Select homoisoflavonoids have promise as antiangiogenic agents that are not generally cytotoxic.

Five previously undescribed compounds, megalocarpoidolide I (1), megalocarpoidolide J (3), 12-epi-crotonzambefuran A (4), megalocarpoidolide K (5), 1-trans-p-hydroxycoumaroyl–geranylgerani-1-ol (6) were isolated from the stem bark of Croton megalocarpoides Friis & M. G. Gilbert. The known ent-trachyloban-18-ol, megalocarpoidolide B, megalocarpoidolide C (2), megalocarpoidolide H, crotocorylifuran, 7,8-dehydrocrotocorylifuran, 1,2-dehydrocrotocorylifuran-2-one, acetyl aleuritolic acid, lupeol, N-trans-p-coumaroyl-3′,4′-dihydroxyphenylethylamine, dodecyl trans-ferulate and lignoceryl trans-ferulate were also isolated. The structures of the compounds were determined using NMR, IR spectroscopy and HRMS. The structure of compound 1 was determined using Logic for Structural Determination (LSD). Compounds 1, 2 and 3 that were selected for screening based on their ability to add diversity to the NCI small molecule compound collection, were evaluated against the NCI60 panel of human tumour cell lines at 10μM level but found to be inactive.

Downy mildew caused by the oomycete Plasmopara viticola is the most devastating pathogen of grapevine. In this study, extracts of the bark of eight important northern forestry species were screened to find extracts showing activity against this pathogen and to identify the active compounds. Extracts from all eight species showed activity against P. viticola, the most promising, dichloromethane extracts of three Larix species, almost completely protecting grapevine from downy mildew under semi-controlled conditions. Five promising lead compounds were isolated: larixol, larixyl acetate, lariciresinol and lariciresinol acetate from Larix species and 7α,15-dihydroxydehydroabietic acid from Pinus sylvestris. These compounds showed 90%-100% efficacy. Larixol and larixyl acetate or 7α,15-dihydroxydehydroabietic acid are present in significant amounts in Larix or P. sylvestris bark extracts, respectively. The identified active compounds are gained from a renewable resource potentially available in large quantities at relatively low prices, making them interesting candidates for the development of a plant-derived fungicide active against a key pathogen in agriculture, providing an opportunity to the forest industry to transform low value by-products into high value-added, bioactive extracts.

A C-25 terpenoid, pseudopulchellol, a rare example of a compound formed by the combination of a monoterpenoid and a sesquiterpenoid unit, was isolated along with eudesm-4(15)-en-1β,6α-diol, its likely precursor, and nine known compounds, including six ent-kaurenoic acids, from the leaves of Croton pseudopulchellus. The Logic for Structure Determination (LSD) protocol was used to determine that pseudopelchellol consisted of the sesquiterpene, eudesm-4(15)-ene-6α-ol, attached at the C-1β position to C10 of the monoterpene, α-pinene. The Electronic circular dichroism (ECD) studies were used to assign the absolute configuration of pseudopulchellol.

Five compounds, 3,4’-dihydroxy-3’,5,5’-trimethoxydihydrostilbene, 1, 3,4'-dihydroxy-3',5'-dimethoxydihydrostilbene, 2, 3,4'-dihydroxy-5,5'-dimethoxydihydrostilbene, 3, 9,10-dihydro-2,7-dihydroxy-4,6-dimethoxyphenanthrene, 4, and the previously unreported 1,2,6,7-tetrahydroxy-4-methoxyphenanthrene, 5, were isolated from the South American orchid, Brasiliorchis porphyrostele. An in depth analysis of their vascular effects was performed on in vitro rat aorta rings and tail main artery myocytes. Compounds 1-4 were shown to possess vasorelaxant activity on rings pre-contracted by the α1 receptor agonist phenylephrine, the CaV1.2 stimulator (S)-(-)-Bay K 8644, or depolarised with high K+ concentrations. However, compound 5 was active solely on rings stimulated by 25 mM but not 60 mM K+. The spasmolytic activity of compounds 1 and 4 was significantly affected by the presence of an intact endothelium. The KATP channel blocker glibenclamide and the KV channel blocker 4-aminopyridine significantly antagonised the vasorelaxant activity of compounds 4 and 1, respectively. In patch-clamp experiments, compounds 1-4 inhibited Ba2+ current through CaV1.2 channels in a concentration-dependent manner, whereas neither compound 4 nor compound 1 affected K+ currents through KATP and KV channels, respectively. The present in vitro, comprehensive study demonstrates that Brasiliorchis porphyrostele may represent a source of vasoactive agents potentially useful for the development of novel antihypertensive agents that has now to be validated in vivo in animal models of hypertension.

The phytochemistry of two Madagascan Crinum species, Crinum hardyi Lehmiller and Crinum pronkii Lehmiller were investigated and compared to that of Crinum firmifolium Baker which has been investigated previously. In addition to hippadine, lycorine, hippeastrine, masonine and crinine from C. firmifolium, lycorine, crinine, and 6-hydroxycrinamine from Crinum hardyi and lycorine, 6-hydroxycrinamine and pseudolycorine from C. pronkii, the novel lycorine-relatediminium salt, the 6,7,11b,11c-didehydrolycorinium salt, was isolated from bulbs of both C. firmifolium and C. hardyi.

Nine triterpenoid derivatives were isolated from the heartwood of X. rumphii and were identified as xylorumphiins E (1), C (2), L (3), and M-R (4-9). Compounds 4-9 have a hemiacetal group in the triterpenoid sidechain making them impossible to purify. Purification was achieved after acetylation and subsequent separation of the epimeric mixtures of acetates, however differentiaition of the R and S epimers was not possible using standard NMR techniques. In one case, the relative configuration of a remotely located stereocenter with respect to the stereocenters in the main skeleton was unambiguously determined using residual dipolar couplings (RDCs). Dipolar couplings were collected from the sample oriented in compressed poly (methyl methacrylate) (PMMA) gels swollen in CDCl3. In another case, the relative configuration was determined using 1D selective quantitative NOE experiments. Xylorumphiin K (10), xyloccensin E, taraxer-14-en-3-ol, (22S)-hydroxytirucalla-7,24-diene-3,23-dione and 25-hydroxy-(20S,24S)-epoxydammaran-3-one were isolated from the bark of the same plant. Compounds 3-10 are new compounds. Compounds 1-6 and xyloccensin E were tested at one concentration, 1 x 10-5 M, in the NCI59 cell one-dose screen but did not show significant activity.

The genus Rhodocodon (Hyacinthaceae sensu APG II) is endemic to Madagascar and its phytochemistry has not been described previously. The phytochemistry of three species in this genus has been investigated and eight compounds, including three bufadienolides (compounds 1, 4, and 5), a norlignan (2), and four homoisoflavonoids (compounds 3 and 6-8) have been isolated and identified. Compounds 1-3 and 6-8 have not been described previously. The COX-2 inhibitory activity of compound 6 and compound 7 acetate (compound 7A) were investigated on isolated colorectal cancer cells. Compounds 6 and 7A inhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 M compared to 12% for 1 mM aspirin (the positive control).

The phytochemistry of both bulbs and seeds of the ethnomedicinal Crinum stuhlmannii subsp. delagoense (Amaryllidaceae) was studied, sourced from a single location simultaneously. Eight alkaloids, including two previously unreported ones, N-methyl-haemanthamide (nivanine), and N-methyl-ent-delagoenine, were isolated along with lycorine, 8,9-methylenedioxophenanthridine, 6-hydroxycrinamine, 6-ethoxycrinamine, haemanthamine and hamayne. Compounds isolated were tested for acetylcholinesterase inhibition.

The stem bark and root bark extracts of Croton dictyophlebodes (Euphorbiaceae) yielded seven undescribed ent-clerodanes: 15,16-epoxy-17,12(S)-olide-ent-cleroda-1,3,13(16),14-tetraen-18-oic acid methyl ester (crotodictyo A), 3β,4β:15,16-diepoxy-ent-cleroda-13(16),14-dien-20-al (crotodictyo B), 3β,4β:15,16-diepoxy-ent-cleroda-13(16),14-dien-19,20-dioic acid (crotodictyo C), 3β,4β:15,16-diepoxy-ent-cleroda-13(16),14-dien-20,19-olide (crotodictyo D), 3β,4β:15,16-diepoxy-20,12(R)-olide ent-cleroda-13(16),14-dien-19-oic acid methyl ester (crotodictyo E), 15,16-epoxy-ent-cleroda-3,13(16),14-trien-12-oxo-18-oic acid (crotodictyo F) and 15,16-epoxy-ent-cleroda-1,3,13(16),14-tetraen-12-oxo-18-oic acid (crotodictyo G), in addition to 15,16-epoxy- ent-cleroda-3,13(16),14-trien-12-oxo-18-oic acid methyl ester (crotodictyo H), reported previously as a synthetic derivative, and acetyl aleuritolic acid. The root extract yielded two ent-trachylobanes, ent-trachylobane-18,19-diol, the undescribed ent-trachylobane-2α,19-diol, along with ent-kaur-16-en-19-oic acid and 2-methoxybenzyl benzoate. Compounds were evaluated against the NCI 60 panel of human tumour cell lines at a single dose of 10−5 M, but showed no significant activity.

The roots of the endangered medicinal plant Croton megalocarpoides (Euphorbiaceae) collected in Kenya has been investigated. Twenty two compounds has been isolated. Among them twelve new ¬ent-clerodane (1-12) and a new abietane (13) diterpenoid alongside the known crotocorylifuran (4a), two known abietane and four known ent-trachylobane diterpenoids, and the triterpenoids, lupeol and acetyl aleurotolic acid. The structures of the compounds were determined using NMR, HRMS and ECD. The isolated compounds have been evaluated against a series of microorganisms (fungal and bacteria) and also against Plasmodium falciparum, however no activity was observed.

Twelve ent-abietane and two ent-pimarane diterpenoids were isolated from the leaves of Croton mubango Müll. Arg. (Euphorbiaceae) collected in the Democratic Republic of the Congo. 2β-Hydroxy-ent-abieta-7,13-dien-3-one, 15-hydroxy-ent-abieta-7,13-dien-3-one, 13α,15-dihydroxy-ent-abieta-8(14)-en-3-one, 2β,9,13-trihydroxy-ent-abieta-7-en-3-one, 2β,7β-dihydroxy-ent-abieta-8,11,13-trien-3-one, 15-hydroxy-ent-abieta-8,11,13-trien-3-one and ent-pimara-8(14),15-dien-3-one and the ent-forms of the previously reported normal series diterpenoids, ent-abieta-8,11,13-trien-3-one, 7β-hydroxy-ent-abieta-8,11,13-trien-3-one, 3α-hydroxy-ent-abieta-8,11,13-triene, 15-hydroxy-ent-abieta-8,11,13-triene and 6β-hydroxy-ent-abieta-8,11,13-triene are reported here for the first time. Structures were established using HRESIMS, FTIR, NMR, DP4+ probability calculations and by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Ent-pimara-8(14), 15-dien-3-one, showed antiproliferative activity against melanoma (MALME-3M), renal (UO-31) and ovarian cancer cell lines (IGROV1) at a concentration of 10−5 M in the NCI 60 screen.

Two new ent-kauren-19-oic acid derivatives, ent-14S*-hydroxykaur-16-en-19-oic acid and ent-14S*,17-dihydroxykaur-15-en-19-oic acid together with eleven known compounds ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid, 8R,13R-epoxylabd-14-ene, eudesm-4(15)-ene-1β,6α-diol, (-)-7-epivaleran-4-one, germacra-4(15), 5E,10(14)-trien-9β-ol, acetyl aleuritolic acid, β-amyrin, and stigmasterol were isolated from the stem bark of Croton pseudopulchellus (Euphorbiaceae). Structures were determined using spectroscopic techniques. Ent-14S*-hydroxykaur-16-en-19-oic acid, ent-kaur-16-en-19-oic acid, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid and 8R,13R-epoxylabd-14-ene were tested for their effects on Semliki Forest virus replication and for cytotoxicity against human liver tumour cells (Huh-7 strain) but were found to be inactive. Ent-kaur-16-en-19-oic acid, the major constituent, showed weak activity against the Plasmodium falciparum (CQS) D10 strain. © 2012 Phytochemical Society of Europe.

Ten new cembranolides, (-)-(1R*,4R*,10R*)-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (1), (-)-(1S*,4R*,10R*)-1-hydroxy-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (2), (-)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (3), (-)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (4), (+)-(10R*)-cembra-1E,3E,7E,11Z,16-pentaen-20,10-olide (5), (+)-(10R*)-cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olide (6), (+)-(5R*,10R*)-5-methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olide (7), (+)-(1S*,4S*,7R*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (8), (-)-(1S*,4S*,7S*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (9), and (+)-(1S*,4R*,8S*,10R*)-1,4,8-trihydroxycembra-2E,6E,11Z-trien-20,10-olide (10), together with six known compounds, lupeol, 4(15)-eudesmene-1β,6α-diol, α-glutinol, 24-ethylcholesta-4,22-dien-3-one, (+)-(1R*,10R*)-cembra-2E,4E,7E,11Z-tetraen-20,10-olide, and (+)-(1R*,4S*,10R*)-4-hydroxycembra-2E,7E,11Z-trien-20,10-olide (4a), have been isolated from the leaves of Croton gratissimus. The acetyl derivatives of 8 and 4a were evaluated against a chloroquine-sensitive strain of Plasmodium falciparum (D10).

Ethnopharmacological relevance The stem bark of Garcinia livingstonei is used traditionally as a skin lightening agent. Aim of the study To isolate and identify compounds responsible for the observed skin lightening activity of Garcinia livingstonei and to evaluate their cytotoxicity. Materials and methods Constituents of the stem bark and fruits of Garcinia livingstonei were isolated using chromatographic techniques and structures were determined using 1D and 2D NMR and MS analysis. MeWo cells were used to evaluate the cytotoxicity and impact on melanin levels of extracts and compounds isolated, in vitro. Results Twelve known compounds, morelloflavone (1), morelloflavone-7″-sulphate (2), guttiferone A (3), sargaol (4), isojacareubin (5), 6-deoxyisojacareubin (6) and in addition to the common triterpenoids, betulin, betulin aldehyde, lupeol, lupenone, euphol and stigmasterol were isolated in this investigation. Morelloflavone, morelloflavone-7″-sulphate and sargaol, were found to be considerably less cytotoxic and more effective as skin lightening agents than hydroquinone. Conclusions A range of compounds was isolated from the stem bark and fruit of Garcinia livingstonei. Although the bark extract contained the cytotoxic guttiferone A, it was found to be less toxic than hydroquinone, and morelloflavone, the 7″-sulphate derivative and sargaol show potential for development as depigmentation/skin lightening agents.

The bulbs of Ledebouria socialis (Hyacinthaceae) yielded the benzocyclobutene homoisoflavonoid, (R)-2',5-dihydroxy-3',4',7-trimethoxyspiro{2H-1-benzopyran-3-(4H)-9-bicyclo[4.2.0]octa[1,3,5]triene}-4-one, socialinone (1). Ledebouria ovatifolia yielded (2ε,3R)-2,5-dihydroxy-7-methoxyspiro[2H-1-benzopyran-3(4H), 5'(6'H)-cyclobuta[f][1,3]benzodioxol]-4-one (2) and the homoisoflavanone, (E)-3-(3',4'-dihydroxybenzylidene)-5,7-dihydroxychroman-4-one, ovatifolionone (5), the dihydrochalcone, 4,4'-dihydroxy-2',6'-dimethoxydihydrochalcone (3), and xanthone, 1,6-dihydroxy-2,3,5-trimethoxy-8-methyl-9H-xanthen-9-one (4) along with 21 known compounds. Structures were determined using spectroscopic techniques. The anti-inflammatory activities of the homoisoflavonoids and xanthones isolated were evaluated against cyclooxygenase-1 and -2 isoenzymes. (R)-3-(3',4'-Dihydroxybenzyl)-7-hydroxy-5-methoxychroman-4-one (7), (E)-3-(3',4'-dihydroxybenzylidene)-7-hydroxy-5-methoxychroman-4-one (10), 1,3,6-trihydroxy-2-methoxy-8-methylxanthen-9-one (6) and ovatifolionone acetate (5Ac) exhibited significant activity against cyclooxygenase-2 at

Four previously undescribed diterpenoids including two crotofolanes, crotodichogamoin A and B, and two halimanes, crothalimene A and B, a new sesquiterpenoid, and fifteen previously reported compounds, including the crotofolane, crotohaumanoxide, the casbane, depressin, a further seven furanohalimane diterpenoids, three patchoulane and two further cadinane sesquiterpenoids and aleuritolic acid were isolated from the root of Croton dichogamus. Crotodichogamoin B is an important biosynthetic intermediate of the crotofolane class and this is the first report of patchoulene sesquiterpenoids from the genus. Compounds were tested at one concentration, 1x10-5 M, in the NCI59 cell one-dose screen but did not show significant activity snd were also evaluated for their cytotoxicity against Caco-2 cell lines using the neutral red assay. 10-epi-Maninsigin D reduced Caco-2 cell viability at 10, 30 and 100 µM, with values of decreased viability of 28%, 48% and 43% respectively. None of the other tested compounds showed significant activity.

The chloroform and ethyl acetate extracts of the leaves of Teclea natalensis have yielded two furoquinoline alkaloids, 6-[(2,3-epoxy-3-methylbutyl)oxy]-4,7-dimethoxyfuro[2,3-b]quinoline and 4,7-dimethoxy-6-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, and the known alkaloids 4,7-dimethoxy-8-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, flindersiamine and dictamnine.

Bioassay guided fractionation of the dichloromethane extract of the underground parts of Gethyllis ciliaris, using a cyclooxygenase-1 enzyme assay, has resulted in the isolation of the dihydroxydimethylbenzopyran-4-one isoeugenitol 1 (IC50 = 262 μM). The 90% methanolic extract yielded 9Z-octadec-9-enamide 3 and the novel compound isoeugenitol glycoside 2. The structures of the isolated compounds have been assigned on the basis of spectral analysis, including 1D and 2D NMR techniques. © 2006 Elsevier B.V. All rights reserved.

The Hyacinthaceae family (sensu APGII) with approximately 900 species in around 70 genera, plays a significant role in traditional medicine in Africa as well as across Europe and the Middle and Far East. The dichloromethane extract of the bulbs of Massonia pustulata (Hyacinthaceae sensu APGII) yielded two known homoisoflavonoids, (R)-5-hydroxy-3-(4-hydroxybenzyl)-7-methoxy-4-chromanone 1 and 5-hydroxy-3-(4-hydroxybenzyl)-7-methoxy-4-chromone 2 and four spirocyclic nortriterpenoids, eucosterol 3, 28-hydroxyeucosterol 4 and two previously unreported triterpenoid derivatives, (17S,23S)-17α,23-epoxy-3β,22β,29-trihydroxylanost-8-en-27,23-olide 5 and (17S, 23S)-17α,23-epoxy-28,29-dihydroxylanost-8-en-3-on-27,23-olide 6. Compounds 1, 2, 3, and 5 were assessed for cytotoxicity against CaCo-2 cells using a neutral red uptake assay. Compounds 1, 2 and 5 reduced cell viability by 70% at concentrations of 30, 100 and 100 μM respectively. Massonia bifolia yielded three known homoisoflavonoids, (R)-(4’-hydroxy)-5-hydroxy-7-methoxy-4-chromanone 1, (R)-(4’-hydroxy)-5,7-dihydroxy-4-chromanone 7 and (R)-(3’-hydroxy-4’-methoxy)-5,7-dihydroxy-4-chromanone 9, two previously unreported homoisoflavonoids, (E)-3-benzylidene-(3’,4’-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 8 and (R)-(3’,4’-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 10, and a spirocyclic nortriterpenoid, 15-deoxoeucosterol 11. Compounds 1, 1Ac, 7, 8, 9 and 10 were screened for antiangiogenic activity against human retinal microvascular endothelial cells. Some compounds showed dose-dependent antiproliferative activity and blocked endothelial tube formation, suggestive of antiangiogenic activity.

Ethnopharmacological relevance: The Zulu and Xhosa people of South Africa use the stem bark of Cassipourea flanaganii as a skin-lightening cosmetic. Aim of the study: To isolate and identify compounds responsible for the skin lightening properties from the stem bark of Cassipourea flanaganii and to evaluate their cytotoxicity towards skin cells, and potential to treat hyperpigmentation. Materials and methods: Extracts from the stem bark of Cassipourea flanaganii were isolated using chromatographic methods and structures were determined using NMR, IR and MS analysis. The tyrosinase inhibitory activity and the ability to inhibit the production of melanin were determined using human primary epidermal melanocyte cells. Cytoxicity was established using the same melanocytes and a neutral red assay. Results: One previously undescribed compound, ent-atis-16-en-19-al (1) along with the known ent-atis-16-en-19-oic acid (2), ent-atis-16-en-19-ol (3), ent-kaur-16-en-19-oic acid (4), ent-kaur-16-en-19-al (5), ent-manoyl oxide (6), guinesine A (7), guinesine B (8), guinesine C (9), lichenxanthone (10), 2,4-dihydroxy-3,6-dimethyl benzoic acid methyl ester (11), lynoside (12), lupeol (13), β-amyrin (14), docosyl ferulate (15), stigmasterol, sitosterol and sitosterol-O-glucoside were isolated in this investigation. An impure fraction containing compound 3 was acetylated to obtain 19-acetoxy-ent-atis-16-ene (3a). Compounds 10 and 11 are usually isolated from lichen, hence they are possible contaminants of lichen harvested with the bark. Compounds 1, 3a, 5-14 were not significantly cytotoxic to the primary epidermal melanocyte cells (P > 0.05) when compared to the negative and positive controls (DMSO, 0.1% and hydrogen peroxide, 30 wt% in water). Inhibition of tyrosinase was significantly greater with respect to the negative control (P < 0.001) for compounds 3a, 5-8 and 9-10 at 10 M and for compounds 5-8 and 9-10 at 100 M. Compared to hydroquinone (the positive control) at 10µM, the level of inhibition was comparable or to that of compounds 3a, 5, 6, and 8-10 at 10µM, with 9 and 10 showing a greater level of inhibition. Inhibition of melanin was both concentration and time dependent for all compounds tested with higher melanin content at 24 hours compared to 48hrs and at 10mM compared to100 mM at both time points; melanin content was significantly lower for hydroquinone at both time points and concentrations. Conclusions: Compounds 1, 5-14, isolated from Cassipourea flanaganii and the derivative 3a showed low cytotoxicity. All compounds had a clear time and concentration dependent effect on melanin content which did not appear to be dependent on their inhibition of tyrosinase.

Twenty-two homoisoflavanones and structurally related compounds isolated from plants were screened for anti-inflammatory activity. Seventeen compounds were isolated from southern African Hyacinthaceae species, one from the Madagascan gentian Tachiadenus longiflorus Griseb. and four were of synthetic origin. Inhibition of prostaglandin synthesis in cell microsomal fractions was first evaluated, followed by screening for specific inhibition of isolated cyclooxygenase enzymes (COX-1 and COX-2). Six homoisoflavanone and structurally related compounds showed significantly high levels of anti-inflammatory activity in the microsomal fraction assay. Only one compound exhibited a high level of anti-inflammatory activity in the COX-1 enzyme assay and no significant activity was detected in the COX-2 enzyme assay. Biological screening was followed by a computer-based quantitative structure-activity relationship (QSAR) study. The physicochemical descriptors: strain energy, heat of formation, volume, surface area, aqueous phase energy, dipole moment, enthalpy, entropy, molar refractivity, parachor, density, refractive index, surface tension, polarizability, logP, Van der Waals interaction energy, Coulombic interaction energy and nonbonded interaction energy were used to characterize the structures of the homoisoflavanones and structurally related compounds. This study produced three equations with significant prediction values for the anti-inflammatory activity of the compounds investigated. The derived models also provided valuable parameter guidelines for those properties influencing the anti-inflammatory activity of the studied compounds.

The efficient and effective selection of appropriate plants for investigative purposes in a drug discovery program is of crucial importance for a successful outcome. A variety of approaches have been used by researchers with varying levels of success. A variety of different approaches to plant selection are discussed, including the ethnomedicinal approach, some ecological approaches, and the use of combinatorial and computational methodologies.

Three new homoisoflavonoids, (3R)-3,5-dihydroxy-7-methoxy-3-(4’-hydroxybenzyl)-4-chromanone, 4, and its 5-O-β-D-glucopyranoside and 5-O-β-D-gentiobiose derivatives, 5 and 6, along with the known homoisoflavonoids, (3S)-5-hydroxy-7-methoxy-3-(4-methoxybenzyl)-4-chromanone, 1, (3R)-5-hydroxy-7-methoxy-3-(4-methoxybenzyl)-4-chromanone (2) and (3S)-5-hydroxy-7-methoxy-3-(4-hydroxybenzyl)-4-chromanone, 3, were isolated from the bulbs of Ornithogalum dubium Houtt.. In addition, three known cardenolides, 3β-(O-α-L-rhamnoside)-5β,14β-dihydroxy-19-oxocardenolide 7, 3β-(O-α-L-rhamnoside)-5β,11α,14β-trihydroxy-19-oxocardenolide, 8 and 3β-(O-α-L-rhamnoside)-5β,11α,14β,19-tetrahydroxycard-20(22)-enolide, 9, were isolated from Ornithogalum ponticum ‘Sochi’. Yields of homoisoflavonoids were low (0.0002 % - 0.0003 %) so stereospecific synthetic methodology needs further refinement to produce antiangiogenic (3R)-3-benzylchromanones and (3S)-3-hydroxyhomoisoflavonoid analogues for further evaluation. This work confirms that, apart from producing cardenolides, the absolute configuration at C-3 of homoisoflavonoids produced by Ornithogalum is 3R (H-3β) for the 3-benzylchromanones and 3S (3-OH β) for the 3-hydroxy benzylchromanones, in agreement with our earlier reports.

An investigation of the seeds of the Madagascan Meliaceae Quivisia papinae has yielded five mexicanolide group limonoids, together with two known mexicanolide limonoids and two known triterpenoids. Quivisianolide A 9 possesses a hitherto unreported 9alpha,11alpha-epoxide ring, quivisianolide B 10 the corresponding delta(9(11)) double bond, and quivisianone 11 is a 17-keto seco-ring D compound.

Three previously unreported triterpenoids 2α,3β,11α-trihydroxyolean-18-ene 1, 3β-acetoxy,2α,11α- dihydroxyolean-18-ene 2 and 2α-acetoxy,3β,11α-dihydroxyolean-18-ene 3 were isolated from the chloroform extract of aerial parts (leaves and flowers) of Salvia phlomoides collected from the Constantine region in the east of Algeria. Structures were determined using NMR spectroscopy and HR-ESI mass spectrometry. Compounds 1, 2 and 3 were tested against the NCI panel of human tumour cell lines at a single dose of 10 µM. Compound 2 was the most active showing a 38 % growth inhibition against the leukemia RPMI-8226 line.

Little previous phytochemical investigation has been conducted on South African Sterculiaceae species used in traditional medicine. In this study, five species, varying in growth type (small herbs, shrubs and large trees) and traditional usage were investigated. The species screened were Cola greenwayi Brenan, Cola natalensis Oliv., Dombeya burgessiae Gerr. ex Harv., Dombeya cymosa Harv. and Hermannia depressa N.E.Br. Extracts were screened for alkaloids, cardiac glycosides, cyanogenic glycosides, saponins and tannins. The probable presence of bufadienolides in the leaf material of Dombeya burgessiae and Dombeya cymosa was determined. Alkaloids, cyanogenic glycosides and saponins were absent in all the plant material investigated. Tannins were detected in the leaf extract of Cola greenwayi and in the leaves, stems and roots of Hermannia depressa. Extracts were screened for anti-inflammatory and antibacterial activity using the cyclooxygenase-1 (COX-1) inhibition assay and the microdilution antibacterial assay. The ethanol and dichloromethane extracts of Cola greenwayi, Dombeya burgessiae and Dombeya cymosa, and the dichloromethane extracts of Hermannia depressa showed the highest levels of COX-1 inhibition. It is possible that the high levels observed may be due to the presence of tannins in some of the extracts. Generally, all the aqueous extracts exhibited low activity. Similarly, no antibacterial activity was observed with the aqueous extracts, although some mild activity was exhibited with some of the ethanol and ethyl acetate extracts. Following the general phytochemical and pharmacological screening, extracts showing antibacterial activity were further purified using bioassay-guided fractionation. Dombeya rotundifolia (Hochst.) Planch., which was screened in a previous study, was also included in the isolation of active compounds. A bioautographic assay, using Staphylococcus aureus, was used to detect the presence of the antibacterial compounds. These were isolated and identified as fatty acids.

A new sesquiterpene lactone, drypemolundein A and a new friedelane derivative, drypemolundein B, along with seven known compounds have been isolated from the whole stems of Drypetes molunduana Pax and Hoffm. Their structures were established on the basis of one- and two-dimensional NMR, homo- and hetero-nuclear spectroscopic evidence.

The methanol extract of the dried stem bark of Drypetes armoracia Pax & Hoffm. afforded two compounds named drypearmoracein A, (E)-4,5,6,7-tetrahydroxy-2-benzylhept-2-enoic acid and drypearmoracein B, 2,3-dihydroxy-9,10-tetrahydroanthra-1,4-quinone along with five known compounds: friedelan-3 β-ol, friedelin, friedelane-3,7-dione, drypemolundein B and β-stigmasterol. Their structures were established on the basis of spectroscopic analysis and chemical evidence. Two compounds named drypearmoraceins A and B have been isolated from Drypetes armoracia.

An investigation of the seeds of the Madagascan Meliaceae Quivisia papinae has yielded quivisianthone, a novel evodulone group limonoid, together with the known azadiradione and two novel derivatives: 6α-hydroxyazadiradione and 7-deacetyl-7-angeloyl-6α-hydroxyazadiradione. Quivisianthone is the first reported evodulone group limonoid possessing both a ring A lactone and an azadiradione-type ring D. The seeds of the Madagascan Meliaceae Quivisia papinae have yielded quivisianthone, a novel evodulone group limonoid, together with the known azadiradione and two novel derivatives: 6α-hydroxyazadiradione and 7-deacetyl-7-angeloyl-6α-hydroxyazadiradione. Quivisianthone is the first reported evodulone group limonoid possessing both a ring A lactone and an azadiradione-type ring D.

The bark of Ekebergia pterophylla yielded atraric acid, beta-amyrin, beta-amyrone, oleanonic acid, beta-sitosterol, beta-sitosteryl acetate and the novel coumarins, pterophyllins 1 and 2. Extractives of the wood yielded the novel coumarins, pterophyllins 3-5. Lupeol was isolated from the hexane extract of the leaves. (C) 1998 Elsevier Science Ltd. All rights reserved.

The seed of Cedrelopsis grevei (Ptaeroxylaceae) has yielded the known compounds uvangoletin, 5,7-dimethylpinocembrin, cardamonin, flavokawin B, 2′-methoxyhelikrausichalcone, and the novel prenylated chalcones, cedreprenone and cedrediprenone. Cedridiprenone has been shown to exhibit superoxide scavenging properties. The seed of Cedrelopsis grevei (Ptaeroxylaceae) has yielded the known compounds uvangoletin, 5,7-dimethylpinocembrin, cardamonin, flavokawin B, 2′-methoxyhelikrausichalcone, and the novel prenylated chalcones, cedreprenone and cedrediprenone. Cedrediprenone has been shown to exhibit superoxide scavenging properties.

The chloroform extract of the leaves of Momordica foetida has yielded 3β, 7β, 23ξ-trihydroxycucurbita-5,24-dien-19-al, 3β, 7β; 25-trihydroxycucurbita-5,23-dien-19-al and 3β,7β-dihydroxy-25-methoxycucurbita-5,23-dien-19-al and the novel compounds 5β,19-epoxy-25-methoxycucurbita-6,23-diene-3β,19-diol, 5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol, 5β,19-epoxy-19-methoxycucurbita-6,23-diene-3β,25-diol, 5β,19-epoxy-19,25-dimethoxycucurbita-6,23-dien-3β-ol and 5β,19-epoxy-25-methoxy-cucurbita-6,23-dien-3β-ol.

The stem bark of Cedrelopsis grevei Baill. has yielded the first reported examples of 5-prenylated coumarins, cedrecoumarin A and B as well as the known coumarins, cedrelopsin, scoparone, O-methylcedrelopsin and norbraylin, and the known chromones ptaeroglycol and ptaeroxylinol.

Investigations of the stem and root bark of Turraea holstii (Meliaceae) have yielded three novel triterpenoids, holstinone A (21 R,23 R-epoxy-7 α,24 S-dihydroxy-21 α,25-dimethoxyapotirucalla-1,14-dien-3-one), holstinone B (21 S,23 R-epoxy-7 α,24 S,25-trihydroxy-21 β-methoxyapotirucalla-1,14-dien-3-one) and holstinone C (21 R,23 R-epoxy-7 α,24 S,25-trihydroxy-21 α-methoxyapotirucalla-1,14-dien-3-one).

Neural networks have been found to be good general classifiers of the binned C-13 NMR spectra of limonoids and associated extractives from the Meliaceae family. 5 ppm binning of the C-13 NMR spectra was found to be superior to 10 ppm binning. The excellent results obtained by developing the system on real extractives using the 5 ppm binning, revealed that the system developed was robust and general enough to tolerate the inherent problems associated with natural product extraction. Experiments concerning the effect of noise and missing bins were also conducted and documented. A literature-sourced sample set was also added in order to ensure the system was not specifically designed to cope only with the unique data set on which it had been trained.

Turraea nilotica has been found to yield a new protolimonoid, 24,25 epoxy-23-hydroxy-7-tirucallen-3-one, which we name niloticin, together with two closely related compounds. No limonoids were found.

We have investigated the seed limonoids of Trichilia dregeana and obtained the known rohituka-7, an ester related to polystachin, and four new compounds designated dregeana-1 to 4. These were found to be intermediate in oxidation level between rohituka-7 and heudelottin.

The herbaceous genus Clivia Lindl. (Amaryllidaceae) comprises four species, all of which are employed in traditional medicine. Two lesser-known ethnomedicinal members, C. gardenii Hook. and C. caulescens R.A.Dyer are phytochemically characterised, revealing a variety of isoquinoline alkaloids. Hippeastrine, haemanthamine, (11S)-11-hydroxyvittatine, lycorine and sterbergine were isolated from C. caulescens, and haemanthamine, haemanthidine in its free base and quaternary salt form, and the quaternary salt of tazettine from C. gardenii. The traditional use of the genus Clivia in southern Africa is overviewed.

The stem bark of Cedrelopsis gracilis (Ptaeroxylaceae) has yielded three known prenylated coumarins, O-methylalloptaeroxylin, ptaerochromenol and umtatin and the novel pentanortriterpenoids, cedkathryn A and cedkathryn B.

The wood of D. schiffneri has yielded (+)-8-hydroxy-calamenene (1) and schiffnerones A (2) and B (3). The wood of Dysoxylum schiffneri (Meliaceae) has yielded the known (+)-8-hydroxycalamenene, the novel sesquiterpenoid, schiffnerone A (1,5-dihydroxy-1,3,5-bisabolatrien-10-one) and the novel trisnorsesquiterpenoid, schiffnerone B (2-hydroxy-11,12,13-trinor-7-calamenone).

The hexane extract of the bark of Entandrophragma delevoyi yielded the known compounds azadirone, 14β, 15β-epoxyazadirone, 6α-acetoxyazadirone, 6α-acetoxy-14β,15β-epoxyazadirone, 6α-acetoxy-14β,15β-epoxyazadiradione, 3,4- secotirucalla-4(28),7,24-triene-3,21-dioic acid and two novel compounds, delevoyin A (3,4- secotirucalla-4(28),7,24-trien-3-oic acid and delevoyin B (6α-acetoxykihadalactone).

Swinniol (3 β,23-dihydroxylup-20(29)-en-28-al), a new triterpenoid has been isolated along with lupeol, betunal and lup-20(29)-ene-3 β,27-diol from the chloroform extract of the bark of Bersama swinnyi. Oleanolic acid was isolated from the leaves.

Seven alkyl and aryl homologues of O-methylsterigmatocystin (OMST) were synthesised and fed in separate experiments to a mutant of Aspergillus parasiticus capable of converting sterigmatocystin (ST) to aflatoxin B1 (AFB1). Their conversion to AFB1 was followed over a time period and it was found that O-propylsterigmatocystin (OPRST) was converted to AFB1 more rapidly than O-ethylsterigmatocystin (OEST) or OMST or ST itself. The aryl derivative O-benzoylsterigmatocystin (OBzST) was converted at the slowest rate. These results show that alkyl and aryl homologues of OMST may be converted to AFB1, suggesting that the methylation of ST is not an absolute requirement for its conversion to AFB1. It seems likely that whatever enzyme(s) are involved in this process exhibit relative specificity. As to whether alkylation of ST is an obligatory step in AFB1 biosynthesis is neither supported nor disproved as the fungal cells used are presumably capable of methylating ST. The fact that the propyl derivative showed fastest conversion is not necessarily significant as this may be due to faster diffusion of the least polar of the derivatives through the cell membrane.

The bufadienolides, 6β-acetoxy-3β,8β,12β,14β-tetrahydroxybufa-4,20,22-trienolide (12β-hydroxyscillirosidin) ( 1) and 14β-hydroxybufa-4,20,22-trienolide 3β- O-{α- l-rhamnopyranosyl-[(1→4)-β- d-glucopyranosyl]-(1→3)-α- l-rhamnopyranoside} (urginin) ( 2) were isolated from Drimia robusta and Urginea altissima, respectively. 12β-Hydroxyscillirosidin and urginin ( A) were isolated from Drimia robusta and Urginea altissima, respectively. Although alkaloids were previously reported from Urginea altissima, none were isolated in this work.

A dihydrochalcone glucoside and a stilbene rutinoside have been isolated from Guibourtia tessmanii. Phytochemical studies on the stem bark of Guibourtia tessmanii yielded a dihydrochalcone glucoside, 2′,4-dihydroxy-4′-methoxy-6′- O-β-glucopyranoside dihydrochalcone and a new stilbene glycoside, 3,5-dimethoxy-4′- O-(β-rhamnopyranosyl-(1→6)-β- glucopyranoside) stilbene besides the known pterostilbene. Their structures were established on the basis of one and two dimensional NMR spectroscopic techniques, FABMS and chemical evidence.

Dynamic supercritical fluid extraction of the limonoid cedrelone from the ground wood of Cedrela toona (Meliaceae) with pure and modified CO2 is studied. Extracts are collected at regular intervals to investigate the extraction kinetics of this compound. A theoretically derived model that involves extrapolating data obtained from shorter extractions to estimate the amount of cedrelone in ground wood is employed. The estimated quantitative results are found to be similar to exhaustive extractions obtained with liquid hexane and supercritical carbon dioxide modified with methanol. Furthermore, data from the supercritical fluid extractions are fitted to the model to produce a characteristic kinetic curve.

Two bufadienolides, 6β-acetoxy-3β,8β,14β-trihydroxy-12-oxobufa-4,20,22-trienolide ( 1) and 14β-hydroxybufa-3,5,20,22-tetraenolide ( 2) were isolated from Drimia robusta and Urginea epigea, respectively. Two bufadienolides, 6β-acetoxy-3β,8β,14β-trihydroxy-12-oxobufa-4,20,22-trienolide and 14β-hydroxybufa-3,5,20,22-tetraenolide were isolated from the dichloromethane extract of the bulbs of Drimia robusta and the methanol extract of the bulbs of Urginea epigea, respectively. The bulbs of Drimia robusta also yielded several known compounds, 6β-acetoxy-3β,8β,12β,14β-tetrahydroxybufa-4,20,22-trienolide (12β-hydroxyscillirosidin) from the dichloromethane extract and three common aromatic acids, 4-hydroxy-3-methoxybenzoic acid, 3,4-dihydroxybenzoic acid, and trans-3-(4′-hydroxyphenyl)-2-propenoic acid from the ethyl acetate extract.

The genus Nymania has been chemotaxonomically linked to the family Meliaceae by the finding that it produces prieurianin, a complex limonoid characteristic of the subfamily Meliodeae. However, there has been no chemical evidence to link it more specifically to the tribe Turraeeae, in which it is placed. We now report that nymania-1, a characteristic limonoid of Nymania capensis, also occurs in the seed of Turraea obtusifolia. This evidence provides a chemotaxonomic link between the genera Nymania and Turraea. Die genus Nymania is oorspronklik chemotaksonomies met die familie Meliaceae verbind, omdat dit 'n komplekse limonoïed, prieurianin, vervaardig wat 'n kenmerk van die onderfamilie Meliodeae is. Maardaar is nog geen chemiese bewyse om Nymania meer spesifiek met die tribus Turraeeae te verbind nie. Ons berig hierin dat nymania-1, 'n karakteristieke limonoi’ed van Nymania capensis, ook in die saad van Turraea obtusifolia gevind is. Hierdie bewyse verskaf 'n chemotaksonomiese verbintenis tussen die genera Nymania en Turraea.

The bulbs of Ammocharis coranica yielded eight alkaloids: lycorine, acetylcaranine and crinamine, which have been reported previously from A. coranica, 1- O-acetyllycorine, hippadine, 6α-hydroxypowelline and hamayne, which have been reported from other members of the Amaryllidaceae, 1- O-acetyl-9- O-demethylpluviine, which has not been described previously, and the known cycloartane compounds: 24-methylenecycloartan-3β-ol, cycloeucalenol, cycloeucalenone and also 24-methylenepollinastanone, which has not been described previously.

Two new compounds, 11α,20ζ-dihydroxydammar-24-ene-3-one and 3α,11α,20ζ-trihydroxydammar-24-ene, were isolated from the hexane extract of the bark and wood of Astrotrichilia asterotricha. Structures were determined by 1H, 13C and 2D NMR spectroscopy.

The hexane extract of the timber of Entandrophtagma spicatum is shown to contain a new protolimonoid, spicatin, which has been identified as 24-hydroxygrandifoliolenone. The known entandrophragmin and a new ester closely related to bussein were also obtained.

Ekebergia capensis and Ekebergia senegalensis are considered conspecific. A chemical investigation of the bark and wood of two South African śpecimens of E.capensis has not produced compounds similar to the coumarin, ekersenin, found previously in the timber of a specimen of E.senegalensis from Nigeria.

The hexane extract of the seed of Aphanamixis polystacha (Meliaceae) has yielded kihadalactone A and three novel limonoids, rohituka-12, rohituka-13 and rohituka-14. The substitution at C-1 of polystachin has been re-assigned as α.

A phytochemical examination has been made of three botanically isolated Madagascar Meliaceae. It is shown that Capuronianthus and Neobeguea are

Aqueous, ethanolic and ethyl acetate extracts of the bark and leaves of five South African Erythrina species Erythrina caffra, Erythrina humeana, Erythrina latissima, Erythrina lysistemon and Erythrina zeyheri were screened for prostaglandin synthesis-inhibitory and anti-bacterial activity. The bark generally displayed higher activity than the leaves in both bioassays. The highest cyclooxygenase inhibiting activity and anti-bacterial activity was recorded for the ethanol and ethyl acetate bark extracts of E. caffra, E. latissima and E. lysistemon. An anti-bacterial compound, 4′,5,7-trihydroxy-6-prenylisoflavone, was isolated by bioassay-guided fractionation from bark of E. lysistemon.

Extraction of the powdered bark of Aglaia ferruginaea yielded an isoflavanoid, ferrugin, whose novel, bridged ring structure was determined by spectroscopic means.

From the hexane extract of the stem bark of Cedrelopsis grevei (Ptaeroxylaceae) was isolated the triterpenoid derivative, cedashnine, and the quassinoid, cedphiline, along with cedmiline, scoparone, β-amyrin and sitosteryl glucoside. The triterpenoid derivative, cedashnine 1 and the quassinoid, cedphiline 2, together with cedmiline, scoparone, β-amyrin and sitosteryl glucoside have been isolated from the stem bark of Cedrelopsis grevei.

A new tetranortriterpenoid, 11 β,12 β-diacetoxyharrisonin, together with the known atalantolide, obacunone, harrisonin, 12 β-acetoxyharrisonin, pedonin, cneorin R and perforaquassin A have been isolated from the root bark of Harrisonia abyssinica. The structure of the new compound which is based on a rearranged tetranortriterpenoid with a five membered ring-B and a seco ring-A and D was assigned on the basis of extensive NMR studies and X-ray diffraction analysis. In addition, the structure and relative configuration of the known perforaquassin A was confirmed by X-ray diffraction analysis.

This report presents the results of an investigation into the application of micellar electrokinetic capillary chromatography (MECC) for the analysis of limonoid glucosides in a citrus seed extract. MECC based on sodium dodecyl sulphate (SDS) was used to provide highly efficient separations of the closely related structures. A phosphate-borate buffer containing SDS was used to optimize the separation conditions for a mixture containing standard compounds of the glucosides of limonin, obacunone and nomilin. The study showed that MECC analysis of limonoid glucosides requires minimal sample clean-up steps and achieves excellent separations within a relatively short analysis time. The technique developed was used to quantify two limonoid glucosides in a methanol extract of the seeds of Citrus nobilis (nartjie) and Citrus limon (lemon).

Malaria is known as tazo or tazomoka in local terminology in Madagascar. Within the context of traditional practice, malaria (and/or malaria symptoms) is commonly treated by decoctions or infusions from bitter plants. One possible approach to the identification of new antimalarial drug candidates is to search for compounds that cure or prevent malaria in plants empirically used to treat malaria. Thus, it is worth documenting the ethnobotanical data, and testing the antiplasmodial activity of the extractive from plants. We interviewed traditional healers, known locally as ombiasy, at Andasibe in the eastern, rainy part of Madagascar. We recorded details of the preparation and use of plants for medicinal purposes. We extracted five alkaloids from Z. tsihanimposa stem bark, and tested them in vitro against Plasmodium falciparum FCM29. We found that traditional healers treat malaria with herbal remedies consisting of one to eight different plants. We identified and listed the medicinal plants commonly used to treat malaria. The plants used included a large number of species from different families. Zanthoxylum sp (Rutaceae) was frequently cited, and plants from this genus are also used to treat malaria in other parts of Madagascar. From the plant list, Zanthoxylum tsihanimposa, bitter plant endemic to Madagascar, was selected and examined. Five alkaloids were isolates from the stem bark of this plant, and tested in vitro against malaria parasite. The geometric mean IC50 values ranged from 98.4 to 332.1 micromolar. The quinoline alkaloid gamma-fagarine exhibited the strongest antiplasmodial activity. The current use of plants for medicinal purposes reflects the attachment of the Malagasy people to their culture, and also a lack of access to modern medicine. The possible extrapolation of these in vitro findings, obtained with plant extracts, to the treatment of malaria and/or the signs evoking malaria is still unclear. If plants are to be used as sources of novel antimalarial compounds, we need to increase our knowledge of their empirical use to improve plant selection. In the hope of preserving useful resources, we should now gather and record ethnobotanical data in Madagascar, and should try to bridge the gaps between empirics and realism.

Abstract Chemical studies of the CH 2 Cl 2 -MeOH extract of the seeds of GAMBEYA AFRICANA (Baker) Pierre led to the isolation of 15 compounds. Their structures were established on the basis of spectroscopic methods and chemical reactions. They comprised five new fatty acid esters of erythrodiol, [3β-octacosanoyloxy-12-oleanen-28-ol, 3β-triacontanoyloxy-12-oleanen-28-ol, 3β-dotriacontanoyloxy-12-oleanen-28-ol, 3β-tetratriacontanoyloxy-12-oleanen-28-ol and 3β-hexatriacontanoyloxy-12-oleanen-28-ol], one new steroidal glycoside, [3β-O-β-xylopyranosylchondrillasterol] and nine known compounds, (3β-octadecanoyloxy-12-oleanene, 3β-eicosanoyloxy-12-oleanene, 3β-docosanoyloxy-12-oleanene, 3β-acetoxy-12-oleanene, erythrodiol, 28-hydroxy-β-amyrone, chondrillasterol , chondrillasterone and 3β-O-β-glucopyranosylchondrillasterol).

The wood of Ekebergia capensis Sparrm. is used by the local Zulu community in KwaZulu-Natal Province, South Africa to facilitate childbirth. In this investigation, the uterotonic properties of extracts from this tree were evaluated using both pregnant and non-pregnant guinea pig uterine smooth muscle in vitro. The extracts were prepared using water modified supercritical carbon dioxide at 400 atm and 80 oC. As samples of these extracts displayed positive results when screened for uterotonic activity, gravity column chromatography followed by NMR spectroscopy was performed in an attempt to isolate and elucidate the structures of the compounds that were present in the extract. The extract yielded five known compounds of which only two, viz. oleanonic acid and 3- epioleanolic acid, displayed uterotonic activity. Receptor binding assays were subsequently performed with 3- epioleanolic acid to ascertain its mode of action. Bradykinin (30 ng/100 μl) and acetylcholine (1 μg/100 μl) were used as the B2 and cholinergic receptor agonists respectively with icatibant (HOE 140) (30 ng/100 μl) and atropine (60 μ/100 μl) as their corresponding antagonists. 3- epioleanolic acid was observed to mediate its effect through the cholinergic receptor. The results of this study show that two compounds from the extract of this tree possess varying degrees of agonist activity on uterine smooth muscle with minor changes in the molecular structure affecting its intrinsic activity on uterine muscle.

Three triterpenoids, sapelin C, sapelin E acetate and grandifoliolenone, were isolated from the hexane extract of the seed shells of Neobegueae mahafalensis (Meliaceae). The ethyl extract of the seed yielded the known limonoids, methyl angolensate, mexicanolide and khayasin.

The novel limonoid, astrotrichilin, has been isolated from the Madagascan Meliaceae plant Astrotrichilia asterotricha.

Methyl angolensate and capensolactones 1–3 were isolated from the seed of Ekebergia capensis. The hexane extract of the seed of Ekebergia capensis (Meliaceae) yielded the novel limonoids, capensolactones 1–3 and the previously isolated methyl 3α-hydroxy-3-deoxyangolensate. Structures were determined by 2D NMR, mass spectroscopy and chemical methods.

The methanol extract of the seeds of Turraea parvifolia has yielded seven novel triterpenoid derivatives: 12alpha-acetoxyazadironolide, turraparvin A (12alpha-acetoxy-7alpha,23-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,14,20(22)-trien-21,23-olide), turraparvin B (12alpha-acetoxy-7alpha,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,14,20(22)-trien-23,21-olide), turraparvin C (7alpha,12alpha-diacetoxy-21-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,14,20(22)-trien-23,21-olide), 11-epi-21-hydroxytoonacilide, 11-epi-23-hydroxytoonacilide and turraparvin D (12alpha-acetoxy-7alpha-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,14,20(22)-trien-21,23-lactam).

A hexane extract of the wood of Dysoxylum muelleri has yielded 3α-cinnamoyl glabretal, 3α-benzoyl glabretal, 21,24-epoxy-23α,25-dihydroxy-4α,4β,8β-trimethyl-14,18-cyclo-5α,13α,14α,17α-cholestan-3α-cinnamoyl-7α-yl acetate, 21,24-epoxy,23α,25-dihydroxy-4α,4β,8β-trimethyl-14,18-cyclo-5α,13α,14α,17α-cholestan-3α-benzoyl-7α-yl acetate; 21,23-epoxy-21,24,25-trihydroxy-4α,4β,8β-trimethyl-14,18-cyclo-5α,13α,14α,17α-cholestan-3α-cinnamoyl-7α-yl acetate and 21,23-epoxy-21,24,25-trihydroxy-4α,4β,8β-trimethyl-14,18-cyclo-5α,13α,14α,17α-cholestan-3α-benzoyl-7α-yl acetate. A hexane extract of the bark yielded 6α-acetoxy-obacunone acetate.

Bioassay-guided fractionation of dichloromethane extracts of Cyrtanthus suaveolens using the Salmonella/microsome assay (strain TA98) led to the isolation of captan [N-(trichloromethylthio)cyclohex-4-ene-1,2-diccarboximide] at a concentration of 100mg kg−1 of dry plant material. Captan is a pesticide used on a large scale on agricultural and horticultural crops. It is known for its mutagenic, genotoxic and teratogenic effects. Issues of quality and safety of traditional medicinal plants grown commercially in South Africa and the need for the establishment of good agricultural practices are discussed.

Investigations of the stem and root bark of Turraea holstii have yielded the known 1,3-diacetylvilasinin and seven novel limonoids: 11- epi-toonacilin, 11 β,12 α-diacetoxycedrelone, 12- O-methylnimbolinin B, 12 α-acetoxyneotrichilenone, 12 α-acetoxy-7-acetyl-1,2-dihydroneotrichilenone, 12 α-acetoxy-1,2-dihydroneotrichilenone and 11 β-acetoxy-7-acetyl-12 α-hydroxy-1,2-dihydroneotrichilenone. The stereochemistry at C-11 in turraflorins A–C from Turraea floribunda has been revised.

The limonoid, 28-deoxonimbolide, and three protolimonoids, 24 S,25-dihydroxytirucall-7-en-3-one, 3-oxo-tirucalla-7, 24-dien-21-al and 21,24 R-epoxy-25-hydroxytirucall-7-en-3-one were isolated from the leaves and bark of Owenia cepiodora.

Turraea floribunda bark has previously been shown to contain limonoids. We now report on the isolation of three new limonoids, turraflorin A, B and C, from the seed of this plant which are ring A, C and D intact, ring B opened, and contain a Δ 8,30, Δ 14 -diene system.

Masticadienonic acid ( E- and Z-forms), 3α-hydroxy-7,24Z-tirucalladien-26-oic acid and two novel triterpenoids, dysoxylic acids A and B, have been isolated from the hexane extract of the wood and bark of Dysoxylum pettigrewianum. Structures were determined using 1H, 13C and 2D NMR techniques.

The stem bark of Cedrelopsis grevei has yielded β-amyrin and two novel limonoid derivatives, the pentanortriterpenoid, cedmilinol, and the hexanortriterpenoid, cedmiline. Structures were elucidated using NMR analysis and the “Logic for Structure Determination” program. The stem bark of Cedrelopsis grevei has yielded β-amyrin and two novel limonoid derivatives, the pentanortriterpenoid, cedmilinol ( 1), and the hexanortrilerpenoid, cedmiline ( 2). Structures were elucidated using NMR analysis and the “Logic for Structure Determination” program.

The ethyl acetate extract of the leaves of Tapura fischeri yielded four novel phaeophytins, 17 3-ethoxyphaeophorbide a, phaeophytin a-13 2-carboxylic acid, 17 3-ethoxy-phaeophorbide a-13 2-carboxylic acid and 17 3-ethoxyphaeophytin b and the known phaeophytin a. Phaeophorbide a methyl ester was isolated from the hexane extract of the leaves of T. fischeri.

The bulbs of three South African Scilla species have been investigated. Scilla kraussii yielded 5,7-dihydroxy-3-(4-hydroxy-4-methoxybenzyl)chroman-4-one, Scilla dracomontana yielded the novel 5,7-dihydroxy-6-methoxy-3-(3-methoxybenzyl)chroman-4-one and also eucomol and 5,7-dihydroxy-6-methoxy-3-(4-hydroxybenzyl)chroman-4-one. Scilla natalensis again yielded 5,7-dihydroxy-6-methoxy-3-(4-hydroxybenzyl)chroman-4-one and 5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)chroman-4-one.

The hexane extract of the bark of Entandrophragma delevoyi has yielded a novel tetranortriterpenoid, delevoyin C. This compound contains a cyclobutanyl ring incorporating C-19 and a cycloheptanyl ring C including C-30. Gedunin and 11β-Acetoxygedunin were isolated from the hexane extract of the wood.

Supercritical fluid extraction has been directly coupled on-line to a uterotonic bioassay, using guinea pig uterine smooth muscle in vitro. This technique was developed for the detection of uterotonic compounds present in medicinal plants used during pregnancy to induce or augment labour. The direct passage of CO 2 into the muscle chamber led to adiabatic cooling of the physiological fluid and inhibition of muscle contraction. This was alleviated by the construction of a CO 2 reduction interface together with the passage of carbogen which aided in the rapid displacement of excess CO 2. The on-line system was evaluated with four plants ( Clivia miniata (Lindl.) Regel, Ekebergia capensis Sparrm., Grewia occidentalis L. and Asclepias fruticosa L.) that are currently used during pregnancy by some black South African women. Extractions were performed with water modified supercritical CO 2. Fractions of supercritical fluid extracts, obtained by sequentially increasing the pressure from 200 to 300 and 400 atm at constant temperature were transferred directly to the muscle chamber to identify the active fractions. The 400 atm extracts of C. miniata, A. fruticosa and E. capensis displayed maximum uterotonic activity while only the 300 atm extract of G. occidentalis induced uterine muscle contraction. This technique proved to be a safe and sensitive method for analyzing medicinal plants that contain uterotonic substances hence assisting in rapidly validating the uterotonic properties and detecting any toxic effects of these extracts.

Southern Africa is one of two world centres of diversity in the Hyacinthaceae, harbouring approximately half the world's family representatives. Some 368 species in 27 genera are locally represented. Plants are well distributed throughout the region, with a predominance in the Western Cape of South Africa. Some 23 species in nine genera have been phytochemically investigated, revealing compounds belonging to a diverse range of chemical classes. The chemical constituents from plants of this family have been divided into four classes, namely, homoisoflavanones, steroidal compounds, bufadienolides and miscellaneous compounds. A single report on the occurrence of Amaryllidaceae alkaloids in Urginea altissima is questioned following a reinvestigation of this species. Plants are employed for traditional medicinal purposes ranging from the treatment of hangovers, rheumatic fever, sprains and syphilis to cancer. A number of species have been toxicologically assessed following human deaths and livestock losses after ingestion. The bioactivity and ethnobotany of southern African hyacinthacs is reviewed, as is the pharmacology of isolated constituents and crude extracts.

The seeds of Owenia acidula of Owenia venosa were found to contain a simple limonoid and a derivative of the cyclopropane protolimonoid glabretal, which has also been found in the timber of Aglaia ferruginea. The timber of Toona australis was found to contain cedrelone, and the timber seed of Xylocarpus moluccensis ( sensu Mabberley) have been found to contain a rich mixture of limonoids. The chemotaxonomic significance of these results is discussed.

The hexane extract of Neobeguea mahafalensis has yielded a limonoid, neobeguin, which is related to pseudrelone A2.

The bulbs of Scilla nervosa have yielded three novel compounds, 5,7-dimethoxy-3-(4-methoxybenzyl)chroman-4-one, 5-hydroxy-7-methoxy-3-(3-hydroxy-4-methoxybenzyl)-chroman-4-one, 5,7-dimethoxy-3-(4-hydroxybenzyl)chroman-4-one and the known compounds 5-hydroxy-7-methoxy-3-(4-methoxybenzyl)chroman-4-one, ( E)-5,7-dihydroxy-3-(4-hydroxybenzylidene)chroman-4-one, ( E)-resveratrol and ( E)-3,3′,5-trihydroxy-4′-methoxystilbene (rhapontigenin).

The bulbs of the South African Drimia altissima (Asparagaceae or Hyacinthaceae sensu APGII) have yielded a range of previously undescribed bufadienolides, drimianins A–G (1–7), the known bufadienolides bovogenin A (8), 3β-O-β-d-glucopyranosylbovogenin A (9), scillaren F (10), and altoside (11), the known homoisoflavonoid (3S)-3-(4′-methoxybenzyl)-5,6,7-trimethoxychroman-4-one (urgineanin C), the sesquiterpenoids 1β,6α-dihydroxy-4(15)-eudesmene and 6α-hydroxy-4(15)-eudesmen-1-one, polybotrin, adenosine, and 9R-hydroxy-(10E,12Z)-octadecadienoic acid ethyl ester. The bufadienolides isolated were tested at 10 μM in the NCI-60 cancer cell screen, and nine of these were selected for further screening at five concentrations. Drimianins C (3) and E (5) showed activity at the nanomolar level against a number of human cancer cell lines in the NCI-60 screen.

Electro-oxidation reactions using a nickel anode were carried out on the calcium-spent liquor effluent obtained from Sappi Saiccor (formerly South African Industrial Cellulose Corporation) dissolving pulp mill as well as on lignin- and lignan-type compounds previously identified in the effluent. Voltammograms were obtained for each solution in order to identify the oxidation potentials of the compounds to be electro-oxidised. Value-added products such as vanillin and syringaldehyde were identified in the electro-oxidised reaction mixtures using gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). Profiles of the changes in concentration of these compounds were determined as a function of time with maximum concentrations reached within the first half hour. These findings are significant in that few electro-oxidation reactions have been carried out on the effluent of a pulp mill which uses the acid bisulphite pulping process and no results have previously been reported on the electro-oxidation of syringaldehyde. This study contributes to a further understanding of the electro-oxidation of lignin and is of value to the paper and pulp industry at large. Reduction of the organic content of the effluent by electro-oxidation was shown to be possible.

Cyrtanthus breviflorus Harv. is a highly variable bulbous taxon from both moist and dry grasslands of the eastern seaboard region of southern Africa. Amongst at least 42 ethnomedicinal regional amaryllids it is the only species reported to treat intestinal worms. The current investigation, the first to phytochemically profile C. breviflorus, has determined the presence in ethanolic bulb extracts of the four known isoquinoline alkaloids: haemanthamine, crinamine hydrochloride, lycorine and tazettine. From the hexane bulb extract five known lupane triterpenoids were isolated: lupeol, lupenone, glochidone, 3β, 27-dihydroxylup-20(29)-ene and betulinaldehyde. Copyright © NISC Pty Ltd.

Sappi Saiccor is a pulp mill that produces high-grade chemical cellulose (dissolving pulp) from predominantly hardwood timber and is currently the world's largest manufacturer of this type of pulp. Attempts to isolate pure lignosulphonates were unsuccessful; however, an acid hydrolysis of the aqueous portion of the calcium effluent stream yielded a range of organic compounds. These included lignans, lignin-type precursors as well as small quantities of vanillin and syringaldehyde. The structures of these compounds were determined using NMR spectroscopic and mass spectrometric techniques.

Dried leaves of the widespread African ethnomedicinal herb Acmella caulirhiza (Asteraceae) have been phytochemically characterised. The hexane extract yielded two unsaturated alkylamides, spilanthol and a novel compound tentatively identified as N-isobutylnona-2E, 4E-dien-8-ynamide based on 1H, 13C, COSY and HETCOR spectra. The occurrence of these amides supports the validation of documented traditional usage patterns. Copyright © NISC Pty Ltd.

Three closely-allied ethnomedicinal Haemanthus (Amaryllidaceae) species from the summer-rainfall region of South Africa have been phytochemically investigated and have yielded a range of isoquinoline alkaloids. H. albiflos yielded homolycorine, albomaculine and the O-methyl-lycorenium salt. From H. pauculifolius, homolycorine, the novel paucamine present as a salt, and the quaternary salts of homolycorine, montanine and manthidine were isolated. H. deformis yielded coccinine, montanine and the quaternary salt of manthidine. Copyright © NISC Pty Ltd.