Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents.
Ramesh R, Shingare RD, Kumar V, Anand A, B S, Veeraraghavan S, Viswanadha S, Ummanni R, Gokhale R, Srinivasa Reddy D.
The structural similarity between an MmpL3 inhibitor BM212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index.