Novel aryloxy azolyl chalcones with potent activity against Mycobacterium tuberculosis H37Rv

A series of twenty seven novel aryloxy azolyl chalcones were synthesized and evaluated in vitro for the growth inhibition of Mycobacterium tuberculosis H37Rv. Ten compounds from this series exhibited good activity with MIC in the range of 3.12–0.78 μg/mL and six of them were found non-toxic against VERO cells and MBMDMøs (mouse bone-marrow derived macrophages), were further evaluated ex-vivo for their potential to kill intracellular bacilli. Two compounds 4 and 19 showed 99% and 71% killing respectively, of intracellular bacilli in MBMDMøs infection model. Further, compound 19, an imidazolyl chalcone with a 2,4-difluorobenzyloxy moiety also exhibited moderate in vivo activity in mice against virulent M. tuberculosis, thus providing a new structural lead towards TB drug development.

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► Aryloxy azolyl chalcones identified as promising inhibitors of M. tuberculosis.
► Benzyloxy as well as azolyl moieties are essential for anti-tubercular activity.
► Imidazoles are more potent than triazoles.