Alcaloïdes Indolomonoterpéniques isolés de Rauvolfia caffra Sond et Tabernaemontana penduliflora K. Schum (Apocynaceae): isolement, détermination structurale et activités biologiques

Abstract

This thesis describes the isolation of indole alkaloids from Rauvolfia caffra and Tabernaemontana penduliflora (Apocynaceae) using modern techniques for isolation of natural products (UHPLC-HRMS), and the evaluation of anti-colon cancer, antimicrobial and antiplasmodial properties of some of them. According to these results, extraction of alkaloids was carry out and the fractionation and purification of alkaloidal extract led to the isolation of 08 new compounds along with 24 known ones. All the structures were characterized on the basis of NMR (1D and 2D), UV, and IR, mass (ESI MS; HRESI MS), CD and TDDFT analysis. The MeOH extract of stem bark of R. caffra yielded 02 undescribed monoterpenes indole alkaloids trivially named rauvolfianoids A-B (306-307). In addition, 17 known indole alkaloids were obtained and identified as raucaffricine (56), nortetraphyllicine (47), tetraphyllicine (42), sarpagine(148), lochnerine (141), 10-methoxytetrahydroalstonine (78), isoreserpiline (80), reserpiline (73), melinonine A (315), darcyribeirine (305), 19-epiajmalicine (316), 3-epi-rauvanine (317), yohimbine (100), suaveoline (206), akuammiline (177) , norsuaveoline (207) and 17-O-acetylnortetraphyllicine (46) respectively, on the basis of their physical and spectroscopic data and by comparison with literature data. Phytochemical investigation of the alkaloidal extract of trunk of T. penduliflora led to the isolation of 05 undescribed carboxy-indole alkaloids with the corynanthe skeleton, penduliflorines A-E (308-312) as well as voacangine-N-oxide alkaloid, tabernaemontine (313) along with 07 known alkaloids namely coronaridine (266), voacangine (322), 3-oxocoronaridine (320), 3-oxoheyneanine (319), voachalotine (323), voacristine hydroxyindolenine (321) and voacangine hydroxyindolenine (318). These species known in Cameroon as “Nepumè” (R. caffra) in Bamiléké and “Etoe” (T.penduliflora) in Ewondo are used for the treatment of infectious diseases and malaria. The MeOH extract of the stem bark of Rauvolfia caffra Sond and the EtOH (95%) extract of trunk of Tabernaemontana penduliflora K. Schum (Apocynaceae) were subjected to biological assay. The first extract was evaluated for their antimicrobial against three bacterial strains (Escherichia coli ATCC 35218, Shigella sp and Salmonella sp); the second extract was then evaluated for their antisplasmodial against two strains 3D7 (CQS) and Dd2 (CQR). Some of the isolated compounds were evaluated for antimicrobial and anticancer activities against three bacterial strains (Escherichia coli ATCC 35218, Shigella sp and Salmonella sp) and CRC-related opportunistic pathogens respectively. Moreover they showed no significant antiproliferative effect against HCT 116 cell line (IC50 > 40 μM). Rauvolfianoid .A exhibited potent antibacterial activities with MIC values in the range 6.25–25 μg.mL−1 and were characterized as weak apoptosis inducers in HCT116 human colon carcinoma cell line. Antiplasmodial activity of penduliflorines A-E and voacangine-N-oxide were evaluated against two strains of Plasmodium falciparum 3D7 and Dd2. These compounds showed good in vitro activity. Among them, penduflorine A and tabernaemontine showed significant inhibitory activity against the two strains with IC50 values in the range 1.85–7.88 ug/mL comparable to those of Artemisinin and Chloroquine, and the others exhibited moderate activity.