5-Benzyliden-2-(5-methylthiazol-2-ylimino)thiazolidin-4-ones as Antimicrobial Agents. Design, Synthesis, Biological Evaluation and Molecular Docking Studies.

In this study, we report the design, synthesis, computational and experimental evaluation of the antimicrobial activity, as well as docking studies of new 5-methylthiazole based thiazolidinones. All compounds demonstrated antibacterial efficacy, some of which (, , and exhibited good activity against and The evaluation of antibacterial activity against three resistant strains, MRSA, , revealed that compound showed the best activity, higher than reference drugs ampicillin and streptomycin, which were inactive or exhibited only bacteriostatic activity against MRSA, respectively. Ten out of fifteen compounds demonstrated higher potency than reference drugs against a resistant strain of which appeared to be the most sensitive species to our compounds. Compounds , and applied in a concentration equal to MIC reduced biofilm formation by more than 50%. All compounds displayed antifungal activity, with compound being the most active. The majority of compounds showed better activity than ketoconazole against almost all fungal strains. In order to elucidate the mechanism of antibacterial and antifungal activities, molecular docking studies on Mur B and CYP51 and dihydrofolate reductase were performed. Docking analysis of MurB indicated a probable involvement of MurB inhibition in the antibacterial mechanism of tested compounds while docking to 14α-lanosterol demethylase (CYP51) and tetrahydrofolate reductase of suggested that probable involvement of inhibition of CYP51 reductase in the antifungal activity of the compounds. Potential toxicity toward human cells is also reported.