Design, synthesis, and biological evaluation of <i>m</i>-amidophenol derivatives as a new class of antitubercular agents.
Zhang NN, Liu ZY, Liang J, Tang YX, Qian L, Gao YM, Zhang TY, Yan M.
A series of <i>m</i>-amidophenol derivatives (<b>6a-6l</b>, <b>7a-7q</b>, <b>9a</b>, <b>9b</b>, <b>12a-12c</b>, <b>14</b> and <b>15</b>) were designed and synthesized. Their antitubercular activities were evaluated <i>in vitro</i> against <i>M. tuberculosis</i> strains H37Ra and H37Rv and clinically isolated multidrug-resistant <i>M. tuberculosis</i> strains. Ten compounds displayed minimal inhibitory concentrations (MICs) against <i>M. tuberculosis</i> H37Ra below 2.5 μg mL<sup>-1</sup> and <b>6g</b> was the most active compound (MIC = 0.625 μg mL<sup>-1</sup>). Compounds <b>6g</b> and <b>7a</b> also showed potent inhibitory activity against <i>M. tuberculosis</i> H37Rv (MIC = 0.39 μg mL<sup>-1</sup>) and several clinically isolated multidrug-resistant <i>M. tuberculosis</i> strains (MIC = 0.39-3.125 μg mL<sup>-1</sup>). 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 <i>m</i>-amidophenol as an attractive scaffold for the development of new antitubercular agents.