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