In vitro and ex vivo antitubercular activity of compounds from Zanthoxylum capense
One approach to identify potential anti-tuberculosis drug leads is to screen medicinal plants traditionally used for tuberculosis treatment. By bioassay-guided fractionation, sixteen compounds, with various structural features, were isolated from the roots of the African medicinal plant Zanthoxylum capense (Thunb.) Harv., which is used by traditional healers in Mozambique to treat TB patients. The compounds were evaluated for antimycobacterial activity against different M. tuberculosis strains as well as cytotoxicity towards THP-1 macrophages. A benzophenanthridine type alkaloid and an N-isobutylamide were found to be promising antibactericidal for M. tuberculosis H37Rv with a found MIC of 1.6µg/ml and a low cytotoxicity (IC50 >60µg/ml). In infected macrophages, the benzophenanthridine alkaloid was able to reduce the bacterial survival by almost two log units at a concentration of 6.2µg/ml, 5 days post drug exposure. The promising anti-tubercular activity of the benzophenanthridine alkaloid, both in vitro and ex vivo against mycobacteria, and the low cytotoxicity towards human macrophages suggest its potential as an anti-TB drug scaffold.
Acknowledgements: This study was supported by FCT, Portugal (SFRH/BPD/37179/2007; PEst-OE/SAU/UI4013/2011).