Based on the structure of marine natural products showing some anti-tubercular (bacteriostatic) activity, we identified small molecules that exhibit bactericidal activity against Mycobacterium tuberculosis and other pathogens. The core structure of the molecules has several stereogenic centers. Antibacterial effect of our new compounds on Mycobacterium smegmatis cells, including persisters, is potentiated during cell transition to stationary phase.
The work will have a substantial synthetic component that will include stereo- and enantioselective synthetic of the bioactive small molecules. The compounds will be screened for in vitro activity against clinical MDR strains of Mycobacterium tuberculosis, from which lead compounds will be identified. We shall also aim to understand the mechanism by which the small molecules disrupt and/or combat mycobacterial persistence.
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