Design and synthesis of some novel hybrid molecules based on 4-thiazolidinone bearing pyridine-pyrazole scaffolds: molecular docking and molecular dynamics simulations of its major constituent onto DNA gyrase inhibition.

Abstract

Due to multidrug resistance, microbial infections have become significant on a global level. As infections caused by several resistant bacteria and fungi severely harm mankind, scientists have developed new antibiotics to combat these infections. In order to develop novel antimicrobial agents, a series of 4-thiazolidinone-based 5-arylidene hybrids (5a-o) have been designed and synthesized to evaluate their antibacterial and antifungal activities. For the determination of the structure of a novel synthesized hybrid, various spectral techniques, e.g., IR, 1H NMR, 13C NMR, and Mass spectroscopy, were used. Two bacterial gram-negative (Escherichia coli and Pseudomonas aeruginosa), two gram-positive strains (Staphylococcus aureus and Streptococcus pyogenes), and one fungal strain (Candida albicans) were used to evaluate antimicrobial activity. Compounds 5c, 5g, and 5i were effective due to their MIC values of 62.5μg/mL against tested bacterial strains (S. pyogenes (5c), P. aeruginosa (5g), and E. coli (5i), respectively.) and 250μg/mL against C. albicans fungal strains, respectively. Additionally, molecular docking and 100ns molecular dynamic simulations were carried out to investigate the stability of molecular contacts and to establish how the newly synthesized inhibitors fit together in the most stable conformations.