Synthesis, Computational, and Photophysical Probing Interactions of Novel Isatin-Incorporated Thiazolyl-Coumarins as Potent Antitubercular Agents

Abstract

In this work, we reported the synthesis of a novel series of isatin-incorporated thiazolyl-coumarin derivatives 4(a–h) by a one-pot three-component reaction of substituted isatin, thiosemicarbazide, and 3-(2-bromoacetyl) coumarin. The structures of the coumarin-thiazole scaffolds were precisely established by their IR, NMR, and HRMS spectral data. The UV–Vis absorption study of target molecules was investigated in six different solvents. Geometrical optimization, molecular electrostatic potential regions, and quantum chemical parameters were assessed using density functional theory (DFT) to explore the electronic properties of thiazolyl-coumarin derivatives. The synthesized compounds were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis; all derivatives exhibited excellent antitubercular efficacy with MIC ? 3.25 µg/mL; among them, 4c and 4f were the most potent with a MIC of 1.56 µg/mL. Furthermore, in silico molecular docking analyses against the enoyl-ACP reductase (InhA) enzyme were conducted; all target ligands demonstrated favorable binding interactions within the active site of the InhA enzyme. © 2025 Wiley-VCH GmbH.