Premium
Synthesis and Evaluation of Aryl/Heteroaryl Benzohydrazide and Phenylacetamide Derivatives as Broad‐Spectrum Antibacterial Agents
Author(s) -
Yele Vidyasrilekha,
Mohammed Afzal Azam,
Wadhwani Ashish D.
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202002178
Subject(s) - benzothiazole , chemistry , aryl , docking (animal) , combinatorial chemistry , stereochemistry , lipinski's rule of five , in silico , antibacterial activity , in vitro , bacteria , organic chemistry , biochemistry , biology , medicine , alkyl , genetics , nursing , gene
A 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 ( Sa ParE). Molecular dynamic simulation of 50 ns was used to find out the stability of predicted binding conformation of 3 c / Sa ParE. 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.