Synthesis, characterization and in silico studies of novel multifunctional imidazole-thiazole hybrids with potent antimicrobial and anticancer properties

Treating infections remains a significant challenge, driving the ongoing pursuit of novel drug candidates. Heterocyclic compounds, such as those containing imidazole and thiazole rings, are well-known for their diverse therapeutic and pharmaceutical applications. In this study, we designed, synthesized, and characterized a series of six novel compounds incorporating these two five-membered rings. The synthesis involved the reaction of different phenacyl bromides with imidazole-hydrazinecarbothioamide to produce imidazole-thiazole hybrid derivatives, which were confirmed through IR, ¹H NMR, ¹³C NMR, and mass spectrometry analyses. The antimicrobial activities of the derivatives were evaluated against three bacterial strains and one fungal strain using the serial dilution method, with their minimum inhibitory concentrations (MICs) determined. Notably, all the derivatives exhibited moderate antimicrobial activity. Cytotoxicity assessment revealed that derivative 5a was particularly excellent, displaying significant inhibition with an IC₅₀ value of 33.52 μM. Furthermore, molecular docking, ADME, and molecular dynamics simulations were conducted, focusing on the interaction between derivative 5a and the protein (PDB ID: 6LUD) to elucidate the stability of the interaction.