Pyridine appended 2-hydrazinylthiazole derivatives: design, synthesis, <i>in vitro</i> and <i>in silico</i> antimycobacterial studies

Abstract

An array of pyridine appended 2-hydrazinylthiazole derivatives has been synthesized to discover novel chemotherapeutic agents for <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). The drug-likeness of pyridine appended 2-hydrazinylthiazole derivatives was validated using the Lipinski and Veber rules. The designed thiazole molecules have been synthesized through Hantzsch thiazole methodologies. The <i>in vitro</i> antimycobacterial studies have been conducted using Luciferase reporter phage (LRP) assay. Out of thirty pyridine appended 2-hydrazinylthiazole derivatives, the compounds 2b, 3b, 5b, and 8b have exhibited good antimycobacterial activity against <i>Mtb</i>, an H37Rv strain with the minimum inhibitory concentration in the range of 6.40-7.14 μM. In addition, <i>in vitro</i> cytotoxicity of active molecules has been observed against Human Embryonic Kidney Cell lines (HEK293t) using MTT assay. The compounds 3b and 8b are nontoxic and their cell viability is 87% and 96.71% respectively. The <i>in silico</i> analyses of the pyridine appended 2-hydrazinylthiazole derivatives have been studied to find the mode of binding of the active compounds with KasA protein of <i>Mtb</i>. The active compounds showed a strong binding score (-5.27 to -6.23 kcal mol^-1).