Chemotaxonomic approach

Ongoing project

Antiprotozoal anthranoids

The genus Psorospermum used in Cameroonian traditional medicine in the treatment of parasitic diseases, is phytochemically explored. Our work focuses on anthranoids bearing the anti-protozoal activity. A structure-activity relationship study is being conducted to identify the pharmacophore, using naturally occuring, semi-synthetic and synthetic anthranoids. Proteomics tools are also being developed to locate and identify the targets of these compounds in the parasites of interest.

Trigocherrierin A, a potent inhibitor of Chikungunya virus replication

Molecules, 2014, 19(3):3617-3627

Abstract : 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).

Graphical abstract

Prostratin and 12-O-tetradecanoylphorbol-13-acetate are potent and selective inhibitors of Chikungunya virus replication

Journal of Natural Products, 2012, 75(12):2183-2187

Abstract : A chemical study of the Vietnamese plant species Trigonostemon howii led to the isolation of a new tigliane-type diterpenoid, trigowiin A (1), along with several known coumarins and phenylpropanoids. The planar structure and the relative configuration of compound 1 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Trigowiin A (1) exhibited moderate antiviral activity in a virus-cell-based assay for Chikungunya virus (CHIKV). Since the structure of compound 1 is closely related to those of well-known tigliane diterpenoids such as prostratin (2), phorbol (3), 12-O-tetradecanoylphorbol 13-acetate (TPA) (4), and 4α-TPA (5), the antiviral activity of the latter compounds was also evaluated against CHIKV, as well as in virus-cell-based assays of two additional members of the genus Alphavirus (Sindbis virus, SINV, and Semliki forest virus, SFV). Whereas prostratin inhibited CHIKV replication with a moderate EC50 of 2.6 μM and a selectivity index (SI) approximating 30, compound 4 proved to be an extremely potent inhibitor, with an EC50 of ∼3 nM and a SI near 2000. Interestingly, no or very little activity was observed on the replication of SINV and SFV.

Graphical abstract

Antiprotozoal Activities of Some Constituents of Markhamia tomentosa (Bignoniaceae)

Annals of Tropical Medicine and Parasitology, 2010, 104:391-398

Abstract : Phytochemical investigation of an ethyl-acetate extract of the stem bark of Markhamia tomentosa (Bignoniaceae), which had good antimalarial activity in vitro, resulted in the isolation of eight known compounds: 2-acetylnaphtho[2,3-b]furan-4,9-dione (1), 2-acetyl-6-methoxynaphtho[2,3-b]furan-4,9-dione (2), oleanolic acid (3), pomolic acid (4), 3-acetylpomolic acid (5), tormentic acid (6), beta-sitosterol (7) and beta-sitosterol-3-O-beta-D-glucopyranoside (8). The structures of these compounds were established by spectroscopic methods. Each of compounds 1, 2, 4 and 5 was evaluated in vitro for its antiprotozoal activities against the ring stages of two chloroquine-resistant strains of Plasmodium falciparum (K1 and W2), the amastigotes of Leishmania donovani, and the bloodstream trypomastigotes of Trypanosoma brucei rhodesiense (the species responsible for human malaria, visceral leishmaniasis and African trypanosomiasis, respectively). Although compounds 1 and 2 exhibited potent antiprotozoal activities, they also showed high toxicity against a mammalian (L-6) cell line.