Design, synthesis, and biological evaluation of m-amidophenol derivatives as a new class of antitubercular agents.

A series of m-amidophenol derivatives (6a-6l, 7a-7q, 9a, 9b, 12a-12c, 14 and 15) were designed and synthesized. Their antitubercular activities were evaluated in vitro against M. tuberculosis strains H37Ra and H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains. Ten compounds displayed minimal inhibitory concentrations (MICs) against M. tuberculosis H37Ra below 2.5 μg mL(-1) and 6g was the most active compound (MIC = 0.625 μg mL(-1)). Compounds 6g and 7a also showed potent inhibitory activity against M. tuberculosis H37Rv (MIC = 0.39 μg mL(-1)) and several clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.39-3.125 μg mL(-1)). The compounds did not show inhibitory activity against normal Gram-positive and Gram-negative bacteria. They exhibited low cytotoxicity against HepG2 and RAW264.7 cell lines. The results demonstrated m-amidophenol as an attractive scaffold for the development of new antitubercular agents.