Triazole-diindolylmethane conjugates as new antitubercular agents: synthesis, bioevaluation, and molecular docking.
Danne AB, Choudhari AS, Chakraborty S, Sarkar D, Khedkar VM, Shingate BB.
We describe the synthesis of novel triazole-incorporated diindolylmethanes (DIMs) using a molecular hybridization approach. The <i>in vitro</i> antitubercular activity of the DIMs against <i>Mycobacterium tuberculosis</i> H37Ra (ATCC 25177) was tested in the active and dormant state. Among all the synthesized conjugates, the compounds <b>6b</b>, <b>6f</b>, <b>6l</b>, <b>6n</b>, <b>6q</b>, <b>6r</b>, and <b>6s</b> displayed good antitubercular activity against both the active and dormant <i>Mtb</i> H37Ra strain. The compound <b>6l</b> exhibited good antitubercular activity against dormant <i>Mtb</i> H37Ra with an IC<sub>50</sub> value of 1 μg mL<sup>-1</sup> and IC<sub>90</sub> (MIC) value of 3 μg mL<sup>-1</sup>. The compounds <b>6b</b>, <b>6l</b>, and <b>6r</b> displayed good antitubercular activity against active <i>Mtb</i> H37Ra with IC<sub>50</sub> values of 2.19, 1.52, and 0.22 μg mL<sup>-1</sup>, respectively. The compounds <b>6b</b>, <b>6h</b>, <b>6l</b>, and <b>6s</b> displayed more than 70% inhibition against the Gram-positive <i>Bacillus subtilus</i> strain at 3 μg mL<sup>-1</sup>. The molecular docking study showed the binding modes of the titled compounds in the active site of the DprE1 enzyme and assisted with elucidating a structural basis for the inhibition of <i>Mycobacteria</i>.