Preparation and in vitro evaluation of benzylsulfanyl benzoxazole derivatives as potential antituberculosis agents

A set of 2-benzylsulfanyl derivatives of benzoxazole was synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria and multidrug-resistant M. tuberculosis. The activities were expressed as the minimum inhibitory concentration (MIC) in mmol/L. The substances showed similar activity against all tested strains. The lead compounds in the set, dinitro derivatives exhibited significant activity against both sensitive and resistant strains of M. tuberculosis and also against non-tuberculous mycobacteria. To facilitate drug design of benzoxazole as potential antituberculosis agent, we have explored the quantitative structure–activity relationship (QSAR). We demonstrated that lower lipophilicity has significant contribution to activity. Dinitrobenzylsulfanyl derivative of benzoxazole represents the promising small-molecule synthetic antimycobacterials.

Graphical abstractSynthesis of a series of 2-benzylsulfanyl derivatives of benzoxazole and their antimycobacterial activities in vitro against sensitive and drug-resistant strains is presented. Dinitro and thioamide derivatives are showed to be the most active compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide