Vincent Dumontet

New nitrogenous and aromatic derivatives from Aglaia argentea and A. forbesii

Seeds and leaves of Aglaia argentea and bark of A. forbesii were extracted. The known cyclopentatetrahydrobenzofuran derivative rocaglaol (1) and the aminopyrrolidine odorine (5), were isolated together with nine new compounds: didesmethylrocaglamide (6), aglains A (7), B (8) and C (9), aglaforbesins A (10) and B (11), ethylrocaglaol (12) and forbaglins A (13) and B (14). Compounds 7–11 and 13,14 possess a new cyclopentatetrahydrobenzopyran and benzoxepine skeleton, respectively, linked to an odorine type moiety. All the structures were elucidated notably by 2D NMR spectroscopy. In addition, the structure of forbaglin A was established by X-Ray crystallographic analysis. Didesmethylrocaglamide revealed strong cytotoxic activity against KB cells (IC50 0.006 μg/ml).

Traditional plants used for medicinal purposes by local communities around the Northern sector of Kibale National Park, Uganda

ETHNOPHARMACOLOGICAL RELEVANCE The study was done to establish medicinal plants used in the treatment of various diseases by the people in the Northern sector of Kibale National Park in western Uganda. It was also aimed at establishing the plant parts used and the mode of preparation of remedies. These plants create a basis for phytochemical evaluation which can lead to the discovery of biologically active compounds that can be used as starting materials in the development of new drugs targeting selected diseases such as malaria. MATERIALS AND METHODS The required information was obtained using open interviews, semi-structured questionnaires, focus group discussions and transect walks. RESULTS Different medicinal plants (131 species) distributed over 55 families were observed to be used by the local communities around the Northern sector of Kibale National Park. The plants as reported in this paper are used to treat 43 physical illnesses/diseases. The most used parts of the plants are the leaves. Water is the main medium used for the preparation of the remedies which are mostly administered orally. CONCLUSION The people in the study area have a rich heritage of traditional plants that are used in the health care system to treat diseases. These medicinal plants have contributed significantly to several disease therapies. The most common diseases treated are malaria and cough, which are mostly treated by Vernonia amygdalina Del. and Albizia coriaria Welw. respectively. The main sources of medicinal plants include bush land, home gardens, grasslands, and the forest.

Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri

The chemical study of the bark and the wood of Trigonostemon cherrieri, a rare endemic plant of New Caledonia, led to the isolation of a series of highly oxygenated daphnane diterpenoid orthoesters (DDO) bearing an uncommon chlorinated moiety: trigocherrins A-F and trigocherriolides A-D. Herein, we describe the isolation and structure elucidation of the DDO (trigocherrins B-F and trigocherriolides A-D). We also report the antiviral activity of trigocherrins A, B and F (1, 2 and 6) and trigocherriolides A, B and C (7-9) against various emerging pathogens: chikungunya virus (CHIKV), Sindbis virus (SINV), Semliki forest virus (SFV) and dengue virus (DENV).

Alkylated Flavanones from the Bark of Cryptocarya chartacea As Dengue Virus NS5 Polymerase Inhibitors

An in vitro screening of New Caledonian plants allowed the selection of several species with a significant dengue virus NS5 RNA-dependent RNA polymerase (RdRp) inhibiting activity. The chemical investigation of Cryptocarya chartacea led to the isolation of a series of new mono- and dialkylated flavanones named chartaceones A-F (1-6), along with pinocembrin. They were isolated as racemic mixtures and characterized using extensive one- and two-dimensional NMR spectroscopy. Four diastereomers of chartaceone A (1) were separated using chiral HPLC, and their absolute configurations were established by comparison of their experimental and calculated ECD spectra. The dialkylated flavanones, chartaceones C-F (3-6), exhibited the most significant NS5 RdRp inhibiting activity, with IC(50) ranging from 1.8 to 4.2 μM. Chartaceones represent a new class of non-nucleosidic inhibitors of the DENV NS5 RdRp.

Gymnemic Acids Inhibit Hyphal Growth and Virulence in Candida albicans

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine.

Jatrophane Diterpenes as Inhibitors of Chikungunya Virus Replication: Structure–Activity Relationship and Discovery of a Potent Lead

Bioassay-guided purification of an EtOAc extract of the whole plant of Euphorbia amygdaloides ssp. semiperfoliata using a chikungunya virus-cell-based assay led to the isolation of six new (1-4, 9, and 10) and six known (5-7, 8, 11, and 12) jatrophane esters. Their planar structures and relative configurations were determined by extensive spectroscopic analysis, and their absolute configurations by X-ray analysis. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, and HIV-1 and HIV-2 viruses. Compound 3 was found to be the most potent and selective inhibitor of the replication of CHIKV and of HIV-1 and HIV-2 (EC50 = 0.76, IC50 = 0.34 and 0.043 μM, respectively). A preliminary structure-activity relationship study demonstrated that potency and selectivity are very sensitive to the substitution pattern on the jatrophane skeleton. Although replication strategies of CHIK and HIV viruses are quite different, the mechanism of action by which these compounds act may involve a similar target for both viruses. The present results provide additional support for a previous hypothesis that the anti-CHIKV activity could involve a PKC-dependent mechanism.

Elemental and metabolite profiling of nickel hyperaccumulators from New Caledonia.

Leaf material from nine Ni hyperaccumulating species was collected in New Caledonia: Homalium kanaliense (Vieill.) Briq., Casearia silvana Schltr, Geissois hirsuta Brongn. & Gris, Hybanthus austrocaledonicus Seem, Psychotria douarrei (G. Beauvis.) Däniker, Pycnandra acuminata (Pierre ex Baill.) Swenson & Munzinger (syn Sebertia acuminata Pierre ex Baill.), Geissois pruinosa Brongn. & Gris, Homalium deplanchei (Viell) Warb. and Geissois bradfordii (H.C. Hopkins). The elemental concentration was determined by inductively-coupled plasma optical emission spectrometry (ICP-OES) and from these results it was found that the species contained Ni concentrations from to 250-28,000 mg/kg dry mass. Gas chromatography mass spectrometry (GC-MS)-based metabolite profiling was then used to analyse leaves of each species. The aim of this study was to target Ni-binding ligands through correlation analysis of the metabolite levels and leaf Ni concentration. Approximately 258 compounds were detected in each sample. As has been observed before, a correlation was found between the citric acid and Ni concentrations in the leaves for all species collected. However, the strongest Ni accumulator, P. douarrei, has been found to contain particularly high concentrations of malonic acid, suggesting an additional storage mechanism for Ni. A size exclusion chromatography separation protocol for the separation of Ni-complexes in P. acuminata sap was also applied to aqueous leaf extracts of each species. A number of metabolites were identified in complexes with Ni including Ni-malonate from P. douarrei. Furthermore, the levels for some metabolites were found to correlate with the leaf Ni concentration. These data show that Ni ions can be bound by a range of small molecules in Ni hyperaccumulation in plants.

Dammarane triterpenes and pregnane steroids from Aglaia lawii and A. tomentosa

Three known dammaranes, cabraleone, eichlerianic acid and shoreic acid, together with two new ones, aglinins A and B, were isolated from the bark of Aglaia lawii. A. tomentosa also contained dammarane triterpenes: the known, cabraleone, cabraleadiol 3-acetate, 3-epiocotillol, cabralealactone, cabralealactone 3-acetate and the new aglinins C and D. In addition, two new pregnane steroids, aglatomins A and B, were isolated from A. tomentosa along with the known cytotoxic cyclopentatetrahydrobenzofuran, rocaglaol. The structure of the new compounds was determined by spectral means, essentially 2D NMR experiments.

New cytotoxic flavonoids from Cryptocarya infectoria

Abstract A new dihydrochalcone, two new dihydroflavanones and eight new biflavonoids have been isolated together with cryptocaryone from the cytotoxic methanol extract of Cryptocarya infectoria. The absolute structure of cryptocaryone was established by X-ray analysis of its 8-bromo derivative. The structure of the new compounds were elucidated by spectroscopic means and their absolute stereochemistry was deduced from chemical correlation, circular dichroism data and NOESY experiments. Several compounds displayed significant cytotoxicity and cryptocaryone was shown to possess cytotoxicity towards multi-drug resistant K562-DOX cells.

Trigocherrierin a, a potent inhibitor of chikungunya virus replication

Trigocherrierin A (1) and trigocherriolide E (2), two new daphnane diterpenoid orthoesters (DDOs), and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV) replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC50 = 0.6 ± 0.1 µM, SI = 71.7).