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
Gulraız Ahmad, Nasır Rasool, Muhammad Usman Qamar, Mohammed Mujahid Alam, Naveen Kosar, Tariq Mahmood, Muhammad Imran
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.