Étude chimique et évaluation des activités antibactériennes, antioxydantes et cytotoxiques des écorces du tronc de deux plantes de la famille des Méliaceae : Ekebergia senegalensis et Entandrophragma candollei

Abstract

The present work focuses on the chemical study and evaluation of the antibacterial, radical scavenging and cytotoxic activities of the stem bark of two plants from Meliaceae family: Ekebergia senegalensis and Entandrophragma candollei. The different crude extracts with a methylene chloride/methanol mixture (1:1) obtained from the bark of these plants were fractionated and purified by chromatographic methods leading to the isolation of 30 secondary metabolites. Their structures of the compounds were determined using their spectroscopic (IR,UV, NMR), spectrometric (MS) data, diffractometric (X-ray), the study of their physical properties and followed by comparison of these data with those found in the literature. The compounds isolated during this work belong to several classes of secondary metabolites identified such as: Eleven triterpenoids: lupeol, oleanonic acid, oleanolic acid, 2,3,22,23-tetrahydroxy- 2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene, 2-hydroxymethyl-2,3,22,23- tetrahydroxy-6,10,15,19,23-pentamethy1-6,10,14,18-tetracosatetraene, β-amyrin, 2-hydroxy- α-amyrin, 22-hydroxyhopan-3-ol, 22-hydroxyhopan-3-one, and β-amyrin acetate, the structure of which is confirmed here by X-ray diffraction. odoratone, therefore the structure and the absolute configurations were corrected using NMR data and X-ray diffraction. Five limonoids: including three new derivatives (encandollens C-E) whose absolute configurations around asymmetric carbons were determined by the NOESY experiment and by the X-ray diffraction, obacurone, prieurianin and methylangolensate, the structure of which is confirmed here by X-ray diffraction. Five steroids: β-sitosterol and stigmasterol mixture, β-sitosterol palmitate, β-sitosterol 3-O-β-D-glucopyranoside, β-sitosterol-3-O-β-D-glucoside-6'-O-palmitate. Eight Phenolic compounds: senegalin, a new derivative, 4,6-dimethoxy-5-methylcoumarin, 7-hydroxy-6-methoxycoumarin so the structure of which is confirmed here by X-ray diffraction, 5-(hydroxymethyl)-4-methoxycoumarin, 6-hydroxy-4-methoxy-5-methylcoumarin, 4-hydroxy-3,5-dimethoxylbenzoic acid, epicatechin, and eucryphin. One fatty acid triester: tripalmitin. In order to confirm the cis configuration of its hydroxyls, odoratone underwent acetonidation to produce three new hemi-synthetic derivatives called: odoratonide I-III. Some isolated compounds as well as those obtained by hemi-synthesis of two plants were tested for their antibacterial activity on four strains namely: Bacillus subtilis DSMZ 704,Micrococcus luteus DSMZ 1605, Escherichia coli DSMZ 1058, and Pseudomonas agarici DSMZ 11810. In addition, the free radical Scavenging and cytotoxic activities of the same compounds were tested on the free radical DPPH and the KB3-1 cell line respectively. However, only 4,6-dimethoxy-5-methylcoumarin and 2-hydroxymethyl-2,3,22,23- tetrahydroxy-6,10,15,19,23-pentamethy1-6,10,14,18-tetracosatetraene showed weak inhibitions on B. subtilis (ZOI: 8 mm) and M. luteus (ZOI: 7 mm) respectively. Moreover, only prieurianin and epicatechin exhibited cytotoxic and antioxidant activity with an IC50 (1.47 μM) and IC50 (21 μg / ml) respectively. In addition, a molecular docking between prieurianin and three proteins involved in the development of cancer, namely: human neutrophil collagenase (MMP-8), α,β-tubulin and topoisomerase-1 was carried out. The results of the in silico docking of this compound supported and delivered further insights on its cytotoxicity