Ethnopharmacologic approach

Ongoing project

Antiplasmodial activity of flavones

After the isolation of an active biflavonoid from Campnosperma panamense (Anacardiaceae, IC50 = 480 nM in vitro on P. falciparum), we developed novel simplified synthetic analogs with improved pharmacological and pharmacokinetic profiles. One of them exhibits a partial in vivo antimalarial activity with a reduction of parasitaemia by 45% on day 4. It may enter the pipeline of the next generation of antimalarial. Its mechanism of action is studied through different complementary approaches.

In vitro preliminary study of antiprotozoal effect of four medicinal plants from Benin

Journal of Medicinal Plants Research, 2013, 7:556-560

Abstract : A total of fourteen extracts with different polarity obtained from four species Crataeva religiosa, Baillonella toxisperma, Boswellia dalzielii and Khaya senegalensis, traditionally used in Benin to treat malaria were tested for their in vitro antiprotozoal activity towardsPlasmodium falciparum, Trypanosoma rhodesiense, Trypanosoma cruzi and Leishmania donovani. Selected plants were extracting with cyclohexane, methylene chloride, ethyl acetate, ether diethyl, methanol and ethanol. Tested extracts showed moderate to good antiparasitic effects at two different concentrations (9.6 and 1.6 µg/ml). Many extracts showed appreciable growth inhibition at 9.5 µg/ml. Ethanol extract of B. dalzielii was the most active against T. rhodesiense and L. donovani with growth inhibition percentage of 100 and 95.6%, respectively. Seven out of fourteen extracts also showed interesting growth inhibition percentage from 99 to 87%, on P. falciparum at 9.6 µg/ml. The most interesting activity against L. donovani was observed with the cyclohexane extract of C. religiosa with growth inhibition value of 55% at 1.6 µg/ml.

Trypanocidal activity of diarylheptanoids from Schrankia leptocarpa DC.

South African Journal of Botany, 2012, 83:92-97

Abstract: Schrankia leptocarpa is a medicinal species use traditionally in Benin to treat malaria. A previous study showed interesting antimalarial activity against two strains of Plasmodium falciparum. Phytochemical investigation of S. leptocarpa DC. (Mimosaceae) led to the isolation of two diarylheptanoids (12), three phenolic acid (35), one p-coumaric acid derivate (6) and three flavonoids (79). The structures of the isolated compounds were established by combination of spectroscopic methods. All isolated compounds were tested in vitro for antiprotozoal activity against P. falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani. Compounds 1 and 2 showed trypanocydal and antiplasmodial activities in the micromolar range. Compound 1 showed also strong submicromolar trypanocidal activity against T. b. rhodensiense with an IC50 value of = 0.79 ± 0.3 μM.

In vitro antileishmanial, antiplasmodial and cytotoxic activities of a new ventiloquinone and five known triterpenes from Parinari excels

Pharmaceutical Biology, 2012, 50:801-806

Abstract :

CONTEXT: Parinari excelsa Sabine (Chrysobalanaceae) is an indigenous tree from West and Eastern Africa. This tree is used in Ivory Coast as an antimalaria remedy.

OBJECTIVE: The in vitro antiplasmodial and antileishmanial activities of the stem bark, the leaf and the major compounds from the stem bark were investigated.

MATERIALS AND METHODS: The leaves and stem bark from P. excelsa were separately collected, air-dried and powdered. Two extracts (methylene chloride and methanol) were realized for both powders. Every extract was tested for its antiplasmodial and antileishmanial activities. Only the stem bark crude extracts were fractionated by column chromatography and their major components were analyzed by NMR, HRESIMS and IR methods. The compounds were tested for their antiplasmodial and antileishmanial activities.

RESULTS: The comparison of the IC50 values of the crude extracts were in this order: 3.41 (IC50 of PeBMc) P. falciparum and 5.19 (IC50 of PeBMc) L. donovani. The stem bark crude extracts were the most active against both parasites. Their fractionation leaded to a new ventiloquinone, five triterpenes and one chlorogenic acid. All these compounds were isolated for the first time from P. excelsa. High activities were observed with (3β)-3-hydroxyolean-12-en-28-oic acid (IC50 = 8.2 µM) and 3β-hydroxyolean-5,12-dien-28-oic acid (IC50 = 7.7 µM) against L. donovani. With the antiplasmodial activity, the best activity was observed with 16β-hydroxylupane-1,20(29)-dien-3-one (IC50 = 28.3 µM).

DISCUSSION AND CONCLUSION: These findings demonstrated that the constituents of P. excelsa stem bark have in vitro antiplasmodial and antileishmanial activities

L’ethnopharmacologie et la recherche de molécules antipaludéennes dans la biodiversité ivoirienne, béninoise et camerounaise

Ethnopharmacologia, 2008, 41:62-70

Abstract : Des études ethnopharmacologiques réalisées en Côte d’Ivoire, au Bénin et au Cameroun ont permis de recenser une sélection d’espèces médicinales utilisées traditionnellement comme antipaludique, mais dont l’activité antiparasitaire n’avait pas fait l’objet d’études scientifiques. Parmi les plantes ivoiriennes, 3 espèces ont montré une activité antipaludique très significative in vitro (IC50 < 10 µg/mL) sur la souche multi-résistante de Plasmodium falciparum K1. Dans le même essai, 9 plantes béninoises et 3 plantes camerounaises se sont également montrées très actives, avec des IC50 < 10 µg/mL. Le fractionnement bioguidé des espèces potentiellement les plus intéressantes a permis d’isoler et d’identifier plusieurs composés purs, présentant des activités antipaludiques marquées, à partir de Croton lobatus et de Thalia geniculata. Par ailleurs, certains des extraits et composés purs obtenus à partir de plantes camerounaises ont montré des activités leishmanicides marquées, notamment les guttiférones A et F, isolées respectivement de Symphonia globulifera et de Allanblackia monticola.

New Sphingolipids and other Constituents from Pancovia laurentii

Helvetica Chimica Acta, 2010, 93:2210-2217

Abstract : Phytochemical investigation of the bark and leaves of Pancovia laurentii (Sapindaceae) resulted in the isolation of a new ceramide and a new cerebroside, named pancoviamide (1), and pancovioside (2) respectively, together with six known compounds: uracil,(R)-N-[(1S,2S,3R)-2,3-dihydroxy-1-(hydroxymethyl)heptadec-5-en-1-yl]-2-hydroxytetracosanamide, stigmasta-7,22-dien-3-ol, β-stitosterol, β-sitosterol 3-O-β-D-glucopyranoside, and 2,3-dihydroxypropyl pentadecanoate. The structures of 1 and 2 were determined by means of spectroscopic methods. Compounds 1 and 2 were tested in vitro for their antiprotozoal properties against several protozoa and for their cytotoxicity.

Comparative antiplasmodial, leishmanicidal and antitrypanosomal activities of several biflavonoids

Phytomedicine, 2006, 13(3):176-180

Abstract : The antiplasmodial, leishmanicidal and antitrypanosomal activities of eight natural biflavonoids were estimated in vitro on a chloroquine-resistant strain of Plasmodium falciparum, axenically grown Leishmania donovani amastigotes and Trypanosoma cruzi trypomastigotes and Trypanosoma brucei rhodesiense bloodstream forms. Lanaroflavone showed the highest antiplasmodial activity (IC(50) = 0.48 microM), isoginkgetin was the most active leishmanicidal compound (IC(50) = 1.9 microM), whereas ginkgetin (IC(50) = 11 microM) and isoginkgetin (IC(50) = 13 microM) showed the best antitrypanosomal activity in our assays. The cytotoxicity and the selectivity indices for the most active compounds were also estimated. Lanaroflavone exhibited a high selectivity index value (SI = 159), indicating selective antiplasmodial activity.