Etude chimique des métabolites secondaires de deux plantes médicinales du Cameroun mostuea batesii baker et mostuea thomsonii (oliv) benth (gelsemiaceae) et évaluation de leurs activités anti-tumorale, antibactérienne et antifongique.

Abstract

The interest in natural products with antitumor and antibacterial properties has led us to focus on secondary metabolites from plants from the African biodiversity belonging to the Gelsemiaceae family. Indeed, previous studies on some species of the Mostuea genus, precisely Mostuea brunonii and Mostuea hursuta led to the isolation of molecules with original and complex structures, some of with possess excellent antitumor and antibacterial properties. In the light of these results, we have undertaken pharmaco-chemical investigations of two other species of the same genus namely Mostuea batesii Baker and Mostuea thomsonii, (Oliv.) Benth two Cameroonian medicinal plants used in traditional medicines for the treatment of many ailments such as cancer, malaria... etc. Investigations of the methanolic extracts from the leaves, stems and roots of these two plants, have led to the isolation of 28 pure compounds, using successive liquid chromatography under atmospheric pressure and flash chromatographic techniques in a normal silica gel phase. The structures of these compounds were determined by using mass spectrometry methods such as electronic impact, FAB and ESI as well as IR, 1D and 2D NMR spectroscopy (COSY, HSQC and HMBC). Among the 28 isolated pure compounds, five were revealed to be new derivatives among which three indolo-monoterpenic alkaloids named thomsoniine A, mostueateciine A and mostueatecine B and one quinolinic monoterpenic alkaloid designated thomsoniine B and one triterpenic derivative named mostuetecine C. Of the 23 remaining known compounds, there are two monterpenic quinolinic alkaloids named, 10-hydroxy-camptothecin, camptothecin, eleven pentacyclic triterpenoids: 3-O-β-Dglucopyranosyl- α-amyrin, 3-O-β-D-glucopyranosyl-28-hydroxy-α-amyrin, β-amyrin-28-oic acid, α-amyrin-28-oic acid, 3-O-β-D-glucopyranosyl-α-amyrin, 3-O-β-D-glucopyranosyl-α-amyrin acid, 3-.O-β-D-glucopyranosyl-β-amyrin, β-amyrin, 2α,3α,19α-trihydroxy-24-norurs-4(23),12-dien-28-oic acid, 3β-acetoxy-2α,19α-dihydroxy-24-norurs-4(23),12-dien-28-oique and 2α,3α,19α-trihydroxy-24-norurs-4(23),12-dienoic acid, one gallic acid derivative (acid, 2,3-dihydroxy- 4, 5-dimethylbenzoic), two carbohydrates (sucrose and sorbitol) and four phytosterol derivatives (stigmasterol, 3-O-β-D-glucopyranoside of stigmasterol, β-sitosterol, 3-O-β-D-glucopyranoside of β-sitosterol). Sucrose and 10-hydroxylcamptotecine were subjected to some chemical transformations, including acetylation and methylation, which led to two new derivatives that were fully characterized. Crude extracts and some isolated pure compounds were evaluated for their antitumor activity against KB-3-1 and KB - V1 cervix cancer cell lines as well as for their antibacterial and antifungal activities against six clinical strains, including: three Gram negative bacteria (Escherichia coli (E.c), Pseudomonas aeruginosa (P.a), Providencia stuartii (P.s)), one Gram positive bacteria (Staphylococcus aureus (S.a)) and two fungi (Candida krusei (C.k) and Cryptococcus laurentii (C.l)). The results showed that compounds such as thomsoniine B, camptothecin, acid 2,3,19-trihydroxy-24-norurs-4(23),12-dien-28-oic and acid 3-acetoxy- 2,19-dihydroxy-24-norurs-4(23),12-dien-28-oic at the concentration of 10 μg/ml and an IC50 ranging from 0.0084 to 0.0088 μg/ml, had 95% mortality from two strains of cervical cancer KB-3-1 and KB-V1. Mostueatecine A and acid 3-acetoxy-2,19-dihydroxy-24-norurs- 4(23),12-dien-28-oique quant to it were shown to be active with regard to fungi (Candida krussei) and Gram-negative bacteria (Escherichia coli) with minimum concentration values of inhibition lower than 1 mg/ml.