2-(2-Hydrazinyl)thiazole derivatives: Design, synthesis and in vitro antimycobacterial studies

• Library of 2-(2-hydrazinyl)thiazole derivatives were synthesized and characterized.
• All the compounds evaluated against Mycobacterium tuberculosis, H37Rv, by in vitro assays.
• 2-Pyridine and 2-hydroxyphenyl hydrazinyl compounds showed good anti-TB activities.
• 2-Pyridine containing thiazole derivatives show low cytotoxicity.
• Compound 4d interacts with KasA protein similar to thiolactomycin.

In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis (Mtb), a series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed by considering Lipinski rule. The designed compounds were synthesized, characterized and evaluated for their inhibitory potential against Mtb, H37Rv, by in vitro assay. The compounds, ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and ethyl-2-[(E)-2-[(2-hydroxyphenyl)methylidene]hydrazin-1-yl]-4-methyl-1,3-thiazole-5-carboxylate, 2i showed noticeable inhibitory activity against Mtb, H37Rv with minimum inhibitory concentration (MIC) of 12.5 μM and 25 μM respectively. An attempt has been made to understand the mechanism of action by binding interactions of these molecules with β-ketoacyl-ACP synthase protein through docking studies. The inhibition constants for compounds 4d and 2i were found to be 1.46 μM and 0.177 μM respectively.

A library of novel 2-(2-hydrazinyl) thiazole derivatives were designed, synthesized and their inhibition, cytotoxicity and interactions were evaluated against Mycobacterium tuberculosis, lung cancer cells and KasA protein respectively.Figure optionsDownload as PowerPoint slide