Synthesis of new pyridine-thiazolidin-4-one and pyridine-pyrazole-thiazolidin-4-one conjugates: Molecular modelling and docking as antimicrobial agents

Abstract

A series of new functionalized pyridine-thiazolidin-4-one and pyridine-pyrazole-thiazolidin-4-one conjugates was synthesized. The DFT/B3LYP approach revealed that the synthesized hybrids had a non-planar configuration. Pyridine-thiazolidinone conjugates 5c and 10c, in which the benzene ring was substituted with a nitro group, exhibited the lowest energy gap (ΔEH-L). Moreover, the MICs of hybrids against Gram-positive (S. aureus, S. pneumoniae) and Gram-negative bacteria (E. coli, S. typhimurium), as well as fungi (C. albicans, A. fumigatus), were determined. Inhibition of DNA gyrase was also studied, with IC50 values showing various inhibitory activities. The antibacterial activity of hybrids 5c, 9, and 10c were substantial, with MIC values of 49, 30, and 35 µg/mL, respectively. The binding energies and interaction patterns of the target protein were identified using molecular docking, which revealed that hybrids 10b and 10c had high binding energies, indicating their potential as antibacterial agents.