Abstract
AbstractTuberculosis, caused by Mycobacteriumtuberculosis(Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current combination therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease.Artemisia afrais used traditionally in southern Africa to treat malaria and recently has shown anti tuberculosis activity. This genus synthesizes a prodigious number of phytochemicals, many of which have demonstrated human health effects. Transcriptomic analysis revealed thatA. afraexerts different effects on Mtb compared toA. annuaor the well-known antimalarial artemisinin, suggesting other phytochemicals present inA. afrawith unique modes of action. A biochemometric study ofA. afraresulted in the isolation of a methoxylated flavone (1), which displayed considerable activity against Mtb strain mc26230. Compound1had an MIC of 312.5 μg/mL and yielded no viable colonies after 6 days of treatment. In addition,1was effective in killing hypoxic Mtb cultures, with no viable cultures after 2 days of treatment. This suggested thatA. afrais a source of potentially powerful anti-Mtb phytochemicals with novel mechanisms of action.
Publisher
Cold Spring Harbor Laboratory
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