A coumarin-based analogue of thiacetazone as dual covalent inhibitor and potential fluorescent label of HadA in mycobacterium tuberculosis

ACS Infectious Diseases Journal

A novel coumarin-based molecule, designed as a fluorescent surrogate of a thiacetazone-derived antitubercular agent, was quickly and easily synthesized from readily available starting materials. This small molecule, coined Coum-TAC, exhibited a combination of appropriate physicochemical and biological properties, including resistance toward hydrolysis and excellent antitubercular efficiency similar to that of well-known thiacetazone derivatives, as well as efficient covalent labeling of HadA, a relevant therapeutic target to combat Mycobacterium tuberculosis. More remarkably, Coum-TAC was successfully implemented as an imaging probe that is capable of labeling Mycobacterium tuberculosis in a selective manner, with an enrichment at the level of the poles, thus giving for the first time relevant insights about the polar localization of HadA in the mycobacteria.

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A coumarin-based analogue of thiacetazone as dual covalent inhibitor and potential fluorescent label of HadA in mycobacterium tuberculosis