Design, synthesis, biological evaluation and molecular docking studies of indole-thiazole hybrids with antimicrobial...

Indole-thiazole hybrids represent an important class of heterocyclic compounds with promising biological potential. In this study, a structurally diverse series of indole-thiazole derivatives incorporating different heterocyclic systems was designed and synthesized from an activated cyanomethyl intermediate, with the aim of evaluating their antimicrobial and DPPH radical-scavenging activities together with molecular docking studies. Antimicrobial screening demonstrated that compounds 12 and 13 were the most active against Staphylococcus aureus and Candida albicans, each showing an MIC of 3.125 μg/mL, comparable to the corresponding reference drugs. Compound 7 exhibited the broadest antibacterial activity, with MIC values of 6.25 μg/mL against both S. aureus and Escherichia coli. In the DPPH radical-scavenging assay, compound 6 showed the highest activity among the synthesized derivatives, with an IC₅₀ of 1.5 μg/mL, compared with 0.8 μg/mL for ascorbic acid, followed by compounds 7 and 9 with IC₅₀ values of 2.0 and 2.2 μg/mL, respectively. Moreover, compounds 7, 12, and 13 were subjected to molecular docking against E. coli MurB (PDB: 2Q85) to explore possible ligand-protein interactions and generate hypotheses for subsequent mechanistic investigation. The corresponding docking scores were - 7.9937, -7.3579, and - 5.7472 kcal/mol for compounds 7, 13, and 12, respectively. These findings identify compounds 6, 7, 12, and 13 as promising candidates for further biological and medicinal-chemistry investigation and support continued exploration of the indole-thiazole framework for antimicrobial and DPPH radical-scavenging applications.