Insilco Molecular Docking studies of series of Pyridines

Abstract

A series of structurally diverse compounds (2a–h, 3a–h, 4a–h, and 5a–h) (Fig:1, Table:1,2,3,4) bearing
substituted pyridine rings were evaluated for their binding affinity toward Staphylococcus aureus DNA
gyrase B (PDB ID: 4URM) using molecular docking studies. The docking analysis revealed binding
energies ranging from −6.26 to −8.08 kcal/mol, indicating favorable interactions with the enzyme active
site. Compound 2f exhibited the highest binding affinity (−8.08 kcal/mol) with a low inhibition constant
of 1.19 μM, followed by 3f (−7.95 kcal/mol) and 4f (−7.72 kcal/mol). Hydrogen-bond interactions with
key catalytic residues including SER128, LYS111, ASP81, GLY109, ALA108, and VAL126
significantly contributed to complex stabilization. Halogen-substituted analogues, particularly bromo-
and chloro-containing derivatives, displayed superior docking scores compared with methyl-substituted
analogues, demonstrating the importance of electronic effects in receptor binding. These findings
suggest that halogenated derivatives represent promising lead molecules for the development of novel
antibacterial agents targeting DNA gyrase B.