Acetylene containing 2-(2-hydrazinyl)thiazole derivatives: design, synthesis, and<i>in vitro</i>and<i>in silico</i>evaluation of antimycobacterial activity against<i>Mycobacterium tuberculosis</i>

Abstract

<i>Mycobacterium tuberculosis</i> resistance to commercially available drugs is increasing day by day. To address this issue, various strategies were planned and are being implemented. However, there is a need for new drugs and rapid diagnostic methods. For this endeavour, in this paper, we present the synthesis of acetylene containing 2-(2-hydrazinyl) thiazole derivatives and <i>in vitro</i> evaluation against the H37Rv strain of <i>Mycobacterium tuberculosis</i>. Among the developed 26 acetylene containing 2-(2-hydrazinyl) thiazole derivatives, eight compounds inhibited the growth of <i>Mycobacterium tuberculosis</i> with MIC values ranging from 100 μg ml^-1 to 50 μg ml^-1. The parent acetylene containing thiosemicarbazones showed promising antimycobacterial activity by inhibiting up to 75% of the <i>Mycobacterium</i> at 50 μg ml^-1. In addition, <i>in silico</i> studies were employed to understand the binding mode of all the novel acetylene-containing derivatives against the KasA protein of the <i>Mycobacterium</i>. Interestingly, the KasA protein interactions with the compounds were similar to the interactions of KasA protein with thiolactomycin and rifampicin. Cytotoxicity study results indicate that the compounds tested are non-toxic to human embryonic kidney cells.