A SHORT HYDROPHOBIC PEPTIDE CONJUGATED 3,5- DISUBSTITUTED PYRAZOLES AS ANTIBACTERIAL AGENTS WITH DNA GYRASE INHIBITION

Abstract

Antimicrobial peptides (AMP) are found in majority of living organisms. Their mode of action is unique and different from the conventional antibiotics. Though several classes of antimicrobial peptides have been studied, their mechanism of action against microbes is not yet clearly understood, otherwise it would open up a solid background for further development of new pharmaceutical compounds. The present work describes the synthesis and evaluation of antimicrobial activity of peptide-pyrazole conjugates. The antibacterial potency of these conjugates was evaluated against both Gram positive and Gram negative bacterial strains, increased antibacterial efficacy was found in peptide-pyrazole conjugates compared to peptides alone and simple pyrazole compounds. A molecular docking study revealed that the ligand PH3, PH4, and PH10 is very potent against key proteins. Compounds PH3, PH4, and PH10 bind near the putative binding site of DNA gyrase with the docking score of -6.54, -8.2, and -7.09 kcal/mol.