"Design, synthesis, biological profile and molecular modeling and MD simulation studies of heterocyclic benzimidazole and thiazolidine-4-one based 5-arylidene analogues as prospective antimicrobial agents"

A series of benzimidazole-thiazolidine-4-one based 5-arylidene hybrids (5a-5o) were synthesized by condensa-tion of 3-((1H-benzo[d]imidazol-2-yl)methyl)-2-(4-nitrophenyl)thiazolidin-4-one (4) and derivatives of benzal-dehyde in ethanol (99 %) using sodium ethoxide as a catalytic agent. Structural elucidation of all the synthesized compounds were performed with IR, 1H NMR, 13C NMR, and mass spectrometry. In vitro antimicrobial activity of the title compounds were evaluated against several bacterial and fungal strains. In comparison to standard drugs, compounds 5b, 5d, 5e, and 5g showed significant antibacterial activity, whereas compounds 5b, 5e, and 5i showed excellent antifungal action, according to their biological activity. In addition, molecular docking and molecular dynamics simulations were performed to ascertain the most stable conformation of newly synthesized inhibitors and to evaluate the stability of molecular interactions within E. coli DNA GyrB protein. Over the course of a 100 nanosecond simulation, compound 5g demonstrated a remarkable degree of stability in its interaction with E. coli DNA GyrB protein. These computational insights unveiled the underlying mechanisms governing antibacterial activity, offering a more comprehensive understanding of the compounds' potential for therapeutic use against bacterial infections.