Synthesis and Evaluation of Aryl/Heteroaryl Benzohydrazide and Phenylacetamide Derivatives as Broad‐Spectrum Antibacterial Agents

Abstract

AbstractA series of novel aryl/heteroaryl benzohydrazide (3 a–d) and aryl/heteroaryl phenylacetamide derivatives (5 a–g) were designed, synthesized and characterized by spectral techniques. The synthesized compounds were screened against pathogenic bacteria to assess their in vitro antibacterial properties. From the eleven synthesized compounds, 3 b(0.7 μg/mL) and 3 c(0.6 μg/mL) exhibited potent activity against a panel of organisms especially against S. aureus. Further, time‐kill study confirmed the bactericidal activity of 3 b and 3 c against S. aureus, that may be because of conjoined benzothiazole and benzohydrazide moieties in their structures. Extra‐precision docking and binding free energy calculation were also performed for the title compounds, in which 3 c(‐6.23 kcal/mol) exhibited higher binding affinity against S. aureus ParE (SaParE). Molecular dynamic simulation of 50 ns was used to find out the stability of predicted binding conformation of 3 c/SaParE. Besides, assessment of in silico ADMET properties illustrates that the title compounds were in agreement with Lipinski's rule parameters. The study could offer a unique framework that may lead to the discovery of novel antibacterials.