Oleanolic Acid and other Compounds Isolated from Cordia africana Lam which Inhibit Vancomycin Resistant Enterococcus

Abstract

ABSTRACT Introduction: Treatment of microbial infections has become complicated due to increased resistance of microbes to the current drugs. The current study investigates crude extracts and seven compounds from root and stem bark of Cordia africana Lam. for antimicrobial and cytotoxic activity. Methods: Extraction was done using 50% methanol in dichloromethane, followed by chromatographic separation of compounds, whose structures were established by interpretation of spectroscopic data. The in vitro susceptibility of selected microbes to the crude extracts and pure compounds was determined. Cytotoxicity of 1, 6 and 7 was determined against the drug sensitive, CCRF-CEM and resistant CEM/ADR-5000 cells, with doxorubicin used as the standard. Results: The root bark extract of C. africana yielded six known compounds: oleanolic acid (1), 3-β-lup-20(29)- en-3-ol (2) stigmast-5,22-dien-3β-ol (3), 2-(2Z) -(3-hydroxy-3,7-dimethylocta2,6-dienyl)-1,4-benzenediol (4), 4-hydroxy-3-methoxy- benzaldehyde (5) and 7-hydroxy-4′-methoxyisoflavone (6). The stem bark extract resulted to 1 and 2 alongside, ubiquinone-8 (7) and 1-octacosanol (8). Compound 1 showed moderate activity against Enterococcus faecium (IC50 of 14.44 µg/ mL), with vancomycin being inactive. Compounds 1, 6 and 7 showed cell viability >50% against CEM/ADR5000 and CCRF-CEM cells at 10 µM and therefore were considered inactive. Surprisingly, 1 was relatively more active compared to the standard, with cell viability of 57.93% against CEM/ ADR5000, versus 78.97% for doxorubicin. Conclusion: To the best of our knowledge, this is the first report of the eight compounds from C. africana. The cytotoxicity of 1, 6 and 7 are reported here for the first time. Traditional use of the plant extract in management of various infections may be attributed to presence of 1, which displayed moderate antimicrobial activity.