Facile synthesis of 4-aryl-N-(5-methyl-1H-pyrazol-3-yl)benzamides via Suzuki Miyaura reaction: Antibacterial activity against clinically isolated NDM-1-positive bacteria and their Docking Studies

Abstract

The production of new pyrazole amide derivatives (6a-h) and their potential against New Delhi metallo-β-lactamase-1 (NDM-1) producing bacteria was described in the present manuscript. The 4-bromo-N-(5-methyl-1H-pyrazol-3-yl)benzamide (5) was synthesized via direct amidation of protected 5-methyl-1H-pyrazol-3-amine (3). The target pyrazole amide derivatives (6a-h) were synthesized in moderate to excellent yield via Palladium catalyzed Suzuki cross-coupling of intermediate molecule (5) with different aryl and heteroaryl boronic acids. NMR and Mass Spectrometry were used to characterize the derivatives. The in vitro antibacterial effect against NDM-1-positive Acinetobacter baumannii and Klebsiella pneumoniae of newly synthesized analogues (6a-h) were determined by Agar well diffusion method. Moreover, MIC and MBC values were also evaluated against the tested bacteria. In addition, the Molecular Docking study of pyrazole amide derivatives (6a-h) against the NDM producing A. baumannii was performed to investigate the intermolecular interaction. The binding affinity and their values were compared with L-captopril. The 6b had greatest potential value and was appeared as a promising antibacterial agent.

Keywords

• Pyrazole benzamides
• Suzuki coupling
• Antibacterial
• Molecular Docking