Antioxidant and Cardioprotective Evaluation of Some N-(3-Chloro-2-oxo-4-arylazetidin-1-yl)-2-[(4-oxo-2-aryl-4H-chromen-7-yl)oxy]acetamide Derivatives

Abstract

A series of N-(3-chloro-2-oxo-4-arylazetidin-1-yl)-2-[(4-oxo-2-aryl-4H-chromen-7-yl)oxy]acetamide derivatives [SLP VI 1(a-d)-2(a-d)] were synthesized from 7-hydroxy flavone derivatives through the intermediate Schiff bases. The synthesized compounds were investigated for in vitro antioxidant property by DPPH radical scavenging assay. The title compounds with good antioxidant potency were further evaluated for possible cardioprotective effect by doxorubicin induced cardiotoxicity. All biochemical changes were normalized after oral administration of the test compounds at the dose of 50 μg/kg. The results showed the significant (p < 0.05) increase in antioxidant enzymes catalase and superoxide dismutase in heart tissue homogenates. These observations enable us to conclude that the synthesized derivatives SLP VI 1b, VI 1c, VI 2b and VI 2d have cardioprotective activity against doxorubicin induced cardiotoxicity. Further, an attempt has been made to perform in silico studies on the synthesized compounds to predict the interaction between test ligands and prospective cardiovascular protein targets using molecular docking tools. The title compounds have good binding affinity with MAPkinase P38 and PKCβ cardiovascular targets.