Excelsoside: a new benzylic diglycoside from the leaves of Milicia excelsa.

A new benzylic diglycoside was isolated from the leaves of Milicia excelsa and identified as 3,4-dimethoxybenzyl beta-D-xylopyranosyl (1 --> 2)-beta-D-glucopyranoside (1). It was obtained together with four known secondary metabolites including lupeol acetate (2), ursolic acid (3), triacontyl (E)-ferulate (4), and 2-(3,5-dihydroxyphenyl)benzofuran-5,6-diol (5). Their structures were determined based on their spectroscopic data and by comparison with those reported in the literature.

Elatumic acid: a new ursolic acid congener from Omphalocarpum elatum Miers (Sapotaceae).

A new triterpene diastereomer, 1, of the previously reported 3beta,6beta,19alpha-trihydroxy-urs-12-en-28-oic acid-24-carboxylic acid methyl ester was obtained from the stem bark of Omphalocarpum elatum Miers (Sapotaceae) along with a-amyrin acetate (2), spinasterol (3), spinasterol 3-O-beta-D-glucopyranoside (4), and tormentic acid (5). The structures of the isolates were established on the basis of NMR and mass spectrometric data and by comparison with those previously reported in the literature. Compound 1 showed weak antibacterial activity against E. aerogenes ATCC13048 and EA3, K. pneumoniae ATCC29916, and P aeruginosa; it also displayed moderate cytotoxicity against CCRF-CEM, CEM/ADR5000, and MDA-MB231 cells.

Phosphodiesterase I-inhibiting Diels-Alder adducts from the leaves of Morus mesozygia.

A new 2-arylbenzofuran derivative, (+)-dimethylsmoracin O (1), and three new Diels-Alder type adducts, mesozygins A­C (2­4), in addition to eight known compounds, artonin I (5), chalcomaracin (6), norartocarpetin (7), moracin L (8), mulberrofuran F (9), moracin M (10), moracin C (11), and morachalcone A (12),were isolated from the leaves of Morus mesozygia Stapf. Structures were elucidated by spectroscopic data analyses. Compounds 2-7 displayed a potent phosphodiesterase I inhibitory activity.

Hepatoprotective and antioxidant arylbenzofurans and flavonoids from the twigs of Morus mesozygia.

The chemical investigation of the twigs of Morus mesozygia resulted in the isolation of three new prenylated 2-arylbenzofurans, named moracin KM, LM, and SC (1-3), nine known 2-arylbenzofurans (4-12), and two known flavonoids (13-14). The structures of the new compounds were established as [2'',3'':6,7]-(6-(S)-hydroxymethyl-6-methylpyrano)-2-(3,5-dihydroxyphenyl)benzofuran-5-ol (1), [2'',3'':6,7]-(4,7-dihydro-6-methyloxepine)-2-(3-hydroxy-5-methoxyphenyl)benzofuran-5-ol (2), and [2'',3'':6,7]-(6,6-dimethylpyrano)-2-(3,5-dihydroxyphenyl)benzofuran (3). One of the new compounds, moracin LM (2), displayed modest antioxidant activity, whereas known compounds 4, 13, and 14 showed significant hepatoprotective and antioxidant activities.

Antimicrobial activities of the methanol extract and compounds from Artocarpus communis (Moraceae).

BACKGROUND: Artocarpus communis is used traditionally in Cameroon to treat several ailments, including infectious and associated diseases. This work was therefore designed to investigate the antimicrobial activities of the methanol extract (ACB) and compounds isolated from the bark of this plant, namely peruvianursenyl acetate C (1), α-amyrenol or viminalol (2), artonin E (4) and 2-[(3,5-dihydroxy)-(Z)-4-(3-methylbut-1-enyl)phenyl]benzofuran-6-ol (5). METHODS: The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC), against seven bacterial and one fungal species. RESULTS: The MIC results indicated that ACB as well as compounds 4 and 5 were able to prevent the growth of all tested microbial species. All other compounds showed selective activities. The lowest MIC value of 64 µg/ml for the crude extract was recorded on Staphylococcus aureus ATCC 25922 and Escherichia coli ATCC 8739. The corresponding value of 32 µg/ml was recorded with compounds 4 and 5 on Pseudomonas aeruginosa PA01 and compound 5 on E. coli ATCC 8739, their inhibition effect on P. aeruginosa PA01 being more than that of chloramphenicol used as reference antibiotic. CONCLUSION: The overall results of this study provided supportive data for the use of A. communis as well as some of its constituents for the treatment of infections associated with the studied microorganisms.

Total synthesis, antiprotozoal and cytotoxicity activities of rhuschalcone VI and analogs.

The total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone VI, is described starting from simple and available resorcinol and 4-hydroxybenzaldehyde. Key steps include the solvent-free Aldol syntheses of chalcones, and the successful application of the Suzuki-Miyaura coupling reaction in the synthesis of bichalcones. The present work constitutes a general method for the rapid syntheses of a number of bichalcones related to rhuschalcone VI. Some of the bichalcones showed moderate antiprotozoal activities against Bodo caudatus, a preliminary screening system for antitrypanosomal activities, most of them with little or no cytotoxicity.

Prenylated arylbenzofuran derivatives from Morus mesozygia with antioxidant activity.

Five prenylated arylbenzofurans, moracins Q-U, were isolated from Morus mesozygia (Moraceae). Their structures were elucidated on the basis of spectroscopic evidence. Along with these compounds, 3beta-acetoxyurs-12-en-11-one, marsformoxide, moracin C, moracin M, moracin K, artocarpesin, cycloartocarpesin, morachalcone A were also isolated. Four of the five compounds, (moracins R-U) displayed potent antioxidant activity.

Rotenoid derivatives and other constituents of the twigs of Millettia duchesnei.

Three prenylated rotenoids, elliptol, 12-deoxo-12alpha-methoxyelliptone and 6-methoxy-6a,12a-dehydrodeguelin were isolated from the twigs of Millettia duchesnei, together with the known compounds, 6a,12a-dehydrodeguelin, 6-hydroxy-6a,12a-dehydrodeguelin, 6-oxo-6a,12a-dehydrodeguelin, elliptone, 12a-hydroxyelliptone and eriodictyol. Their structures were elucidated on the basis of spectral data and comparison with information reported in the literature and with authentic specimens for some known compounds. The full NMR data of 6-oxo-6a,12a-dehydrodeguelin and 6-hydroxy-6a,12a-dehydrodeguelin are reported here for the first time.

Antimicrobial activity of the crude extracts and five flavonoids from the twigs of Dorstenia barteri (Moraceae).

The aim of this study was to evaluate the antimicrobial activity of the crude extract of the twigs of Dorstenia barteri (DBT) as well as that of four of the five flavonoids isolated from this extract. Gram-positive bacteria (six species), Gram-negative bacteria (12 species) and fungi (four species) were used. The agar disc diffusion test was used to determine the sensitivity of the tested samples while the well micro-dilution was used to determine the minimal inhibition concentrations (MIC) and the minimal microbicidal concentration (MMC) of the active samples. The results of the disc diffusion assay showed that DBT, isobavachalcone (1), and kanzonol C (4) prevented the growth of all the 22 tested microbial species. Other compounds showed selective activity. The inhibitory activity of the most active compounds namely compounds 1 and 4 was noted on 86.4% of the tested microorganisms and that of 4-hydroxylonchocarpin (3) was observed on 72.7%. This lowest MIC value of 19.06microg/ml was observed with the crude extract on seven microorganisms namely Citrobacter freundii, Enterobacter aerogens, Proteus mirabilis, Proteus vulgaris, Bacillus megaterium, Bacillus stearothermophilus and Candida albicans. For the tested compounds, the lowest MIC value of 0.3microg/ml (on six of the 22 organisms tested) was obtained only with compound 1, which appeared as the most active compound. This lowest MIC value (0.3microg/ml) is about 4-fold lower than that of the RA, indicating the powerful and very interesting antimicrobial potential of isobavachalcone (1). The antimicrobial activities of DBT, as well as that of compounds 1, 3, 4, amentoflavone (5) are being reported for the first time. The overall results provide promising baseline information for the potential use of the crude extracts from DBT as well as some of the isolated compounds in the treatment of bacterial and fungal infections.

Antimicrobial activity of the methanolic extracts and compounds from Treculia obovoidea (Moraceae).

The crude extract from Treculia obovoidea was subjected to purification by repeated chromatography. Eight compounds were isolated from Treculia obovoidea and identified as Psoralen (1), Bergapten (2), 7-methoxycoumarin (3), 7-hydroxycoumarin (4), 4,2',4'-trihydroxychalcone (5), 4,2',4'-trihydroxy-3-prenylchalcone (6), 3-hydroxy-4-methoxybenzoic acid (7) and O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl) butyl] bergaptol (8). These compounds together with the extract were tested for their antimicrobial activity against Gram-positive bacteria (six species), Gram-negative bacteria (12 species) and three Candida species using micro-dilution methods for the determination of the minimal inhibition concentration (MIC) and the minimal microbicidal concentration (MMC). The MIC values obtained with the crude extracts varied from 78.12 to 156.25 microg/ml against 17 (80.95%) of the 21 tested microorganisms. All the isolated compounds showed selective activity. The antimicrobial activity of this plant as well as that of compounds 6 and 8 is being reported for the first time. The obtained results provide promising baseline information for the potential use of these crude extract as well as some of the isolated compounds in the treatment of bacterial and fungal infections.

Prenylated chalcones, flavone and other constituents of the twigs of Dorstenia angusticornis and Dorstenia barteri var. subtriangularis.

The twigs of Dorstenia angusticornis and Dorstenia barteri var. subtriangularis yielded 16 compounds. Two novel diprenylated chalcones: 3,5'-di-(2-hydroxy-3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone, 3, 4-(2,2-dimethylpyrano)-3'-(2-hydroxy-3-methylbut-3-enyl)-2',4'-dihydroxychalcone and the known stipulin were isolated from both species. 3-(2-Hydroxy-3-methylbut-3-enyl)-5'-(3,3-dimethylallyl)-4,2',4'-trihydroxychalcone and the known compounds: 4-hydroxylonchocarpin, kanzonol B, bartericins A, B, C and 3'-(2-hydroxy -3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone were isolated from D. barteri while the known compounds: gancaonin Q, paratocarpins C, F, and lupeol were obtained from Dorstenia angusticornis. beta-Sitosterol and its beta-d-glucopyranoside were isolated from both species. Structures of these secondary metabolites were established using spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HMQC and HMBC.

Revision of the absolute configuration of plumericin and isoplumericin from Plumeria rubra.

The absolute configurations of plumericin (1) and isoplumericin (2), isolated from Plumeria rubra, were re-assigned based on a combination of X-ray crystal-structure determination and quantum-mechanical calculations of their circular dichroism (CD) spectra. The experimental CD spectra showed an excellent match with those calculated for the (1S,5R,8R,9R,10R) absolute configuration (corresponding to ent-1 and ent-2, resp.), opposite to that generally accepted and published in the literature. Since the (false) plumericin configuration has been often used to derive the absolute configuration of related iridoids by chemical correlation, their absolute configurations also have to be reconsidered.

Screening of the Pan-African natural product library identifies ixoratannin A-2 and boldine as novel HIV-1 inhibitors.

The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resource-limited regions of the world.

Homoisoflavonoids and xanthones from the tubers of wild and in vitro regenerated Ledebouria graminifolia and cytotoxic activities of some of the homoisoflavonoids.

Eleven homoisoflavonoids and two xanthones were isolated and characterized from the bulbs of Ledebouria graminifolia. Five of the homoisoflavonoids are new compounds and were identified as: 5-hydroxy-7-methoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-6,7-dimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5,7,8-trimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-3',4',7-trimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one, 5,7-dihydroxy-3',4'-dimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one. Structures were elucidated by extensive 1D, and 2D NMR spectroscopy and HRMS. A method for tissue culture was developed and the bulbs of mature plants were found to contain all the compounds isolated from the wild specimens of L. graminifolia.

Diterpenoids from the stem bark of Croton zambesicus.

Three clerodane diterpenoids, crotozambefurans A, B and C were isolated from the stem bark of Croton zambesicus together with the known clerodane crotocorylifuran and two trachylobanes: 7 beta-acetoxytrachyloban-18-oic acid and trachyloban-7 beta, 18-diol. Betulinol, lupeol, sitosterol and its 3 beta-glucopyranosyl derivative were also obtained. The structures of crotozambefurans A, B and C were determined, respectively, as: 15,16-epoxy-1,3,13(16),14-clerodatetraen-20,12-olide-18,19-dioic acid dimethylester, 15,16-epoxy-1,3,13(16),14-clerodatetraen-18,19,20-trioic acid trimethylester and 15,16-epoxy-3,13(16),14-clerodatrien-19,1 alpha:20,12-diolide-18-oic acid methylester, using spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HSQC, HMBC and TOCSY.

Chalcones and other constituents of Dorstenia prorepens and Dorstenia zenkeri.

The twigs of Dorstenia prorepens furnished the digeranylated chalcone, 5,3'-(3,7-dimethyl-2,6-octadienyl)-3,4, 2',4'-tetrahydroxychalcone while Dorstenia zenkeri yielded the 3',4'-(3-hydroxy-2,2-dimethyldihydropyrano)-4,2'-dihydroxychalcone and a bichalcone. 4-Hydroxylonchocarpin was found in both plants. D. prorepens also yielded the known compounds: psoralen, bergapten, beta-sitosterol and its D-glucopyranosyl derivative. D. zenkeri yielded p-hydroxybenzaldehyde, dorsmanin A, 4,2',4'-trihydroxychalcone and 4,2',4'-trihydroxy-3'-prenylchalcone. Structures of the new compounds were established by UV, IR, MS and 2-D NMR analysis.

Diprenylated chalcones and other constituents from the twigs of Dorstenia barteri var. subtriangularis.

The twigs of Dorstenia barteri var. subtriangularis yielded three diprenylated chalcones: (-)-3-(3,3-dimethylallyl)-5'-(2-hydroxy-3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone, (+)-3-(3,3-dimethylallyl)-4',5'-[2'''-(1-hydroxy-1-methylethyl)-dihydrofurano]-4,2'-dihydroxychalcone and 3,4-(6",6"-dimethyldihydropyrano)-4',5'-[2''',-(1-hydroxy-1-methylethyl)-dihydrofurano]-2'-hydroxychalcone for which the names bartericins A, B and C, respectively, are proposed. Stipulin, beta-sitosterol and its 3-beta-D-glucopyranosyl derivative were also isolated. The structures of these secondary metabolites were determined on the basis of spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HMQC and HMBC. The structural relationship of bartericins B and C was further established by the chemical cyclization of one to the other.

Dinklagins A, B and C: three prenylated flavonoids and other constituents from the twigs of Dorstenia dinklagei.

Three prenylated flavonoids, dinklagins A, B and C identified, respectively, as (-)-6-(3,3-dimethylallyl)-7-hydroxy-6''', 6'''-dimethylchromeno-(4',3',2''',3''')-flavanone, (+)-5,4',5"xi-trihydroxy-6'',6''-dimethylchromano-(7,6,2'',3'')-flavone and (+)6-(2xi-hydroxy-3-methyl-3-butenyl)-5,7,4'-trihydroxyflavone were isolated from the twigs of Dorstenia dinklagei together with the known 6-prenylapigenin, 4-hydroxylonchocarpin, stipulin and 5,4'-dihydroxy-6'',6''-dimethylchromano-(7,6,2'',3'')-flavone. Their structures were determined on the basis of spectral data and by comparison with data reported in the literature and with authentic specimens for known compounds.

Prenylated flavonoids, monoterpenoid furanocoumarins and other constituents from the twigs of Dorstenia elliptica (Moraceae).

A monoprenylated flavan and two monoterpenoid substituted furanocoumarins were isolated from the twigs of Dorstenia elliptica along with 3-(3,3-dimethylallyl)-4,2',4'-trihydroxylchalcone, psoralen, bergapten, O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl)butyl]bergaptol, beta-sitosterol and its beta-D-glucopyranoside. The structure of the flavan was determined as 6(1,1-dimethylallyl)-7,4'-dihydroxylflavan and the monoterpenoid substituted furanocoumarins were assigned as O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl)-3-hydroxybutyl]-bergaptol and O-[2-(5-hydroxy-2,6,6-trimethyl-3-oxo-2H-pyran-2-yl)ethyl]bergaptol, respectively, using spectroscopic analysis, especially, 2D NMR spectra.

Virtualizing the p-ANAPL library: a step towards drug discovery from African medicinal plants.

BACKGROUND: Natural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted. EXPERIMENTAL APPROACH: A current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinski's "Rule of Five" has been used to evaluate likely oral availability of the samples. RESULTS: A majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the "Rule of Five". The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed. CONCLUSIONS AND IMPLICATIONS: The p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns.