Antimicrobial and in silico studies of the triterpenoids of Dichapetalum albidum.

Here we report a new polyhydroxylated triterpene, 2ß,6ß,21α-trihydroxyfriedelan-3-one (4) isolated from the root and stem bark of Dichapetalum albidum A. Chev (Dichapetalaceae), along with six known triterpenoids (1-3, 5, 6, 8), sitosterol-3ß-O-D-glucopyranoside (9), a dipeptide (7), and a tyramine derivative of coumaric acid (10). Friedelan-3-one (2) showed an antimicrobial activity (IC50) of 11.40 µg/mL against Bacillus cereus, while friedelan-3α-ol (1) gave an IC50 of 13.07 µg/mL against Staphylococcus aureus with ampicillin reference standard of 19.52 µg/mL and 0.30 µg/mL respectively. 3ß-Acetyl tormentic acid (5) showed an IC50 of 12.50 µg/mL against Trypanosoma brucei brucei and sitosterol-3ß-O-d-glucopyranoside (9) showed an IC50 of 5.06 µg/mL against Leishmania donovani with respective reference standards of IC50 5.02 µg/mL for suramin and IC50 0.27 µg/mL for amphotericin B. Molecular docking of the isolated compounds on the enzyme glucose-6-phosphate dehydrogenase (G6PDH) suggested 3ß-acetyl tormentic acid (5) and sitosterol-3ß-O-D-glucopyranoside (9) as plausible inhibitors of the enzyme in accordance with the experimental biological results observed.

Antiangiogenic Pterocarpan and Flavonoid Constituents of Erythrina lysistemon.

The roots of Erythrina lysistemon, growing in Egypt, yielded 24 flavonoid compounds, including 17 pterocarpans, two isoflavanones, one flavanone, two isoflavans, one 2-arylbenzofuran, and an isoflava-3-ene. Nine pterocarpans have not been reported previously (7-9, 11-14, 19, and 20), and 11 are reported here for the first time from this species. Structures were established using HRESIMS, NMR, and circular dichroism techniques. Selected compounds were tested for their ability to block the growth of human retinal endothelial cells and antiangiogenic activity in vitro. The isoflavonoids 5 and 6, and the pterocarpans 1, 2, 4, 20, and 22 demonstrated selective antiproliferative activities on endothelial cells compared to a nonendothelial cell type, with concentration-dependent antiangiogenic effects in vitro against HRECs, a cell type relevant to neovascular eye diseases.

Coumarinolignoid and Indole Alkaloids from the Roots of the Hybrid Plant Citrus × paradisi Macfad (Rutaceae).

A phytochemical investigation of the roots of Citrus × 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 µg/mL, respectively, compounds 1-7 showed weak activity, with IC50 values of 99.2 to 250.2 µM and 99.5 to 192.7 µM, respectively.

Antiproliferative Bufadienolides from the Bulbs of Drimia altissima.

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), 3ß-O-ß-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 1ß,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.

The effect of isolates from Cassipourea flanaganii (Schinz) alston, a plant used as a skin lightning agent, on melanin production and tyrosinase inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: The Zulu and Xhosa people of South Africa use the stem bark of Cassipourea flanaganii as a skin-lightning cosmetic. AIM OF THE STUDY: To isolate and identify compounds responsible for the skin lightning properties from the stem bark of Cassipourea flanaganii and to evaluate their cytotoxicity towards skin cells. 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), ß-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 µM and for compounds 5-8 and 9-10 at 100 µM. Compared to hydroquinone (the positive control) at 10 µM, the level of inhibition was comparable or to that of compounds 3a, 5, 6, and 8-10 at 10 µM, 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 h compared to 48 h s and at 10 mM 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.

Ent-clerodane and ent-trachylobane diterpenoids from Croton dictyophlebodes.

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), 3ß,4ß:15,16-diepoxy-ent-cleroda-13(16),14-dien-20-al (crotodictyo B), 3ß,4ß:15,16-diepoxy-ent-cleroda-13(16),14-dien-19,20-dioic acid (crotodictyo C), 3ß,4ß:15,16-diepoxy-ent-cleroda-13(16),14-dien-20,19-olide (crotodictyo D), 3ß,4ß: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.

Cytotoxic diterpenoids from the leaves and stem bark of Croton haumanianus (Euphorbiaceae).

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-3ß-hydroxy-16R-kauran-17-al, ent-16S,17-epoxykauran-19-ol, ent-16S,17-epoxykauran-3ß-ol, ent-17-palmityloxykaurane-3ß,16ß-diol, ent-17-palmityloxykauran-16ß-ol, ent-3α,18-cyclokaurane-16ß,17-diol and 19-nor-16α,17-dihydroxy-ent-kaur-4(18)-ene and three undescribed ent-clerodanes, dimethyl ent-15,16-epoxy-6ß-hydroxy-1,3,13(16),14-clerodatetraen-20,12S-olide-18,19-dioate (saniolide A), dimethyl ent-15,16-epoxy-6ß-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-isopimaranes, ent-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-3ß,16ß,17-triol, ent-17-palmityloxykaurane-3ß,16ß-diol and ent-17-palmityloxykauran-16ß-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.

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels.

Five compounds, 3,4'-dihydroxy-3',5,5'-trimethoxydihydrostilbene, 1: ; 3,4'-ihydroxy-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 α 1 receptor agonist phenylephrine, the CaV1.2 stimulator (S)-(-)-Bay K 8644, or depolarized 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 antagonized 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.

Bufadienolides and anti-angiogenic homoisoflavonoids from Rhodocodon cryptopodus, Rhodocodon rotundus and Rhodocodon cyathiformis.

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.

Ent-abietane and ent-pimarane diterpenoids from Croton mubango (Euphorbiaceae).

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. 2ß-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, 2ß,9,13-trihydroxy-ent-abieta-7-en-3-one, 2ß,7ß-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, 7ß-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 6ß-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.

The Antiangiogenic Activity of Naturally Occurring and Synthetic Homoisoflavonoids from the Hyacinthaceae ( sensu APGII).

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).

Laevifins A-G, clerodane diterpenoids from the Bark of Croton oblongus Burm.f.

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 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, B and G showed moderate activities against the MCF-7 cancer cell line (IC50 102, 115 and 106 µM, respectively) while ß-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.

Pumilol, a Diterpenoid with a Rare Strobane Skeleton from Pinus pumila (Pinaceae).

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 17 known compounds including serratane triterpenoids, not previously reported from this species, and four ferulate derivatives. The absolute configuration of pumilol was established using HR-ESI-MS, NMR, the DP4+ probabilities and by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Labda-8(17),13-dien-15-oic acid (4), bornyl (E)-4-hydroxycinnamate (14) and bornyl (E)-ferulate (15) showed activity against S. aureus and/or E. faecalis with MIC90 values 12.5 - 50 µm.

Antiangiogenic Activity and Cytotoxicity of Triterpenoids and Homoisoflavonoids from Massonia pustulata and Massonia bifolia.

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-3ß,22ß,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.

Reducing copper use in the environment: the use of larixol and larixyl acetate to treat downy mildew caused by Plasmopara viticola in viticulture.

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 optimise the 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 by up to 39% by purification steps. The combined concentration of larixyl acetate and larixol from larch turpentine could be increased by up to 66%. The Minimal Inhibitory Concentration (MIC100 ) against P. viticola in vitro (6-23 µg mL-1 ) and the Effective Concentration (EC50 ) in planta under semi-controlled conditions (0.2-0.4 mg mL-1 ) were promising compared with other plant extracts. In vineyards, efficacies of larch extracts reached up to 68% in a stand-alone strategy and 84% in low-copper strategies. CONCLUSION: Larch extracts represent valid candidates for copper reduction in organic vineyards, and their development into a sustainable plant protection product might be feasible. © 2017 Society of Chemical Industry.

Diterpenoids from the roots of Croton dichogamus Pax.

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, 1 × 10-5 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.

Application of Residual Dipolar Couplings and Selective Quantitative NOE to Establish the Structures of Tetranortriterpenoids from Xylocarpus rumphii.

Nine triterpenoid derivatives were isolated from the heartwood of Xylocarpus 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 side chain, 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. Dipolar couplings were collected from the sample oriented in compressed poly(methyl methacrylate) 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-3ß-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 × 10-5 M, in the NCI59 cell one-dose screen but did not show significant activity.

Phytochemical Investigations of Three Rhodocodon (Hyacinthaceae Sensu APG II) Species.

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) was investigated on isolated colorectal cancer cells. Compounds 6 and 7A inhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 µM compared to 12% for 1 mM aspirin (the positive control).

New ent-Clerodane and Abietane Diterpenoids from the Roots of Kenyan Croton megalocarpoides Friis & M. G. Gilbert.

The roots of the endangered medicinal plant Croton megalocarpoides collected in Kenya were investigated and twenty-two compounds isolated. Among them were twelve new ent-clerodane (1-12) and a new abietane (13) diterpenoids, alongside the known crotocorylifuran (4 a), 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 were evaluated against a series of microorganisms (fungal and bacteria) and also against Plasmodium falciparum, however no activity was observed.

Constituents of Bulbs of three Species of the Hyacinthaceae (Hyacinthoideae): Eucomis vandermerwei, E. zambesiaca and Resnova humifusa.

Phytochemical analyses of the bulbs of Eucomis vandermerwei and E. zambesiaca yielded homoisoflavonoids and triterpenoid derivatives. A new (17S*23S*)-epoxy-3ß,15ß,29-trihydroxy-27-norlanost-8-en-24-one) was isolated from E. zambesiaca. Resnova humifusa yielded homoisoflavonoids, and a tetrahydropyran derivative, 2-methyl-3-(4S*,5R *,7S*-trihydroxy-8S*-hydroxymethyltetrahydro-6H-4-pyranyl)-2-propenoic acid. All compounds were assayed for COX-2 inhibition of cyclooxygenase; 3,5,7-trihydroxy-3-(4'-methoxybenzyl)-4-chromanone was found to have significant activity.