Métabolites Secondaires de deux plantes médicinales Camerounaises à activités antibactériennes : Celtis tessmannii Rendle (Cannabaceae) et Nauclea latifolia Smith (Rubiaceae). Structures, transformations chimiques et évaluations de quelques activités biol

Abstract

This work concerns the valorization of some Cameroonian medicinal plants belonging to traditional pharmacopeia. It’s concentrated on the search of new antibacterial compounds or urease inhibitors involved in virulence and resistance of some bacteria (Helicobacter pylori, Proteus mirabilis, Ureaplasma urealyticum, Haemophilus influenzae...). This result of our studies gives the phytochemical survey of two Cameroonian medicinal plants Celtis tessmannii Rendle (Cannabaceae) and Nauclea latifolia Smith (Rubiaceae), as well as evaluation of the urease inhibitory properties, the antibacterial activities, the anti-inflammatory and the antioxidant activities of isolated compounds and their hemisynthetic derivatives. Compounds were isolated using usual chromatographic methods of separation. The structure of the compounds were established using physical and spectroscopic techniques, including MS, IR, UV, 1 and 2D- NMR (COSY, HSQC, HMBC and NOESY) and by comparison of physical and spectral data with those described in literature. From this survey, 30 compounds were isolated and characterized. The methanol extract of stem bark and roots of Celtis tessmannii Rendle, afforded 17 compounds including 05 phenolic amides (trans-N-coumaroyltyramine, trans-N caffeoyltyramine, trans-N-feruloyloctopamine, trans-N-feruloyltyramine, a mixture of trans N-coumaroyloctopamine and trans-N-caffeoyltyramine); 01 benzoic acid derivative (glucosyringic acid); 01 polyol (1-O-methyl-cis-inositol), 01 diacid (succinic acid), 02 fatty acid (laceroic acid and stearic acid), 01 mixture of sterols (stigmasterol and β-sitosterol) and his glycoside (β-sitosterol-3-O-β-D-glucoside). The neutral fraction of the wood of N. latifolia led to the isolation and characterization of 13 compounds, including 06 pentacyclics triterpenes (3β,6β,19α,23-trihydroxy-olean-12-en-28-oic acid, pomolic acid, 3β,6β,23-trihydroxy-olean 12-en-28-oic acid, quinovic acid, quinovic acid 3-O-β-L-rhamnopyranoside and quafrinoic acid) and 07 alkaloids, among which three are new (latifolianine A, latifoliaindole A and B) and, four known (naucleidinal dimethyl acetal, (+)-naucleofficine D, pobeguinine and naucleidinal). Five derivatives were prepared either by acetylation or O-prenylation in order to increase their lipophicic.Compounds isolated from neutral fraction of heartwood of N. latifolia were evaluated in vitro for their antibacterial properties on Haemophilus influenzae strain and minimum inhibition concentrations ranged from 3.13-50 μg/mL were obtained. Naucleidinal was the most active with a MIC of 3.13 μg/mL. Compounds from C. tessmannii were also tested for their urease inhibiting and antioxidant properties. The compounds tested, showed IC50 > 14.3 μM. The most potent constituent was 1-O-methyl-cis-inositol with IC50 = 14.3 μM compared to thiourea (IC50 = 21.6 μM) used as reference. Succinic acid, trans-N-Thèse de doctorat Ph D rédigée par KAGHO KENOU Donald Ulrich Page feruloyoctopamine and trans-N-feruloyltyramine have shown good level of antioxidant activity with IC50 of 18.5, 16.5, 9.5 μM respectively, and are 2 to 4 times more active than the reference BHA (IC50 = 44.2 μM). In reducing of the free radical’s assays, trans-N-feruloyoctopamine (IC50 = 36.5 μM) and trans-N-feruloyltyramine (IC50 = 30.0 μM) were found to be more active than the reference (BHA, IC50 = 49.8 μM). Succinic acid and glucosyringic acid showed good level of lipoxygenase inhibitory activity with IC50 of 12.9 and 15.1 μM respectively, compared to that of baicalein (IC50 = 22.6 μM) used as reference. Best results for inhibitory urease properties and antibacterial activities were obtained for 1-O-methyl-cis-inositol and naucleidinal respectively from Celtis tessmannii Rendle and Nauclea latifolia Smith. These results validate the uses of these plants in traditional medicine.