In vitro and in silico evaluation of N-(alkyl/aryl)-2-chloro-4-nitro-5- [(4-nitrophenyl)sulfamoyl]benzamide derivatives for antidiabetic potential using docking and molecular dynamic simulations

Abstract

A series of N-(alkyl/aryl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide derivatives were synthesized and evaluated for its in vitro antidiabetic potential against α-glucosidase and α-amylase enzymes and also for its antimicrobial potential. Compounds N-(2-methyl-4-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide and N-(2-methyl-5-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide were found to be the most potent α-glucosidase and α-amylase inhibitors with IC50 values of 10.13 and 1.52 µM, respectively. The docking results depicted reasonable dock score −10.2 to −8.0 kcal/mol (α-glucosidase), −11.1 to −8.3 kcal/mol (α-amylase) and binding interactions of synthesized molecules with respective targets with enzymes. During molecular dynamic simulations, analysis of RMSD of ligand protein complex suggested stability of the most active compound at binding site of target proteins. Compound N-(2-chloro-4-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl] benzamide showed antibacterial potential against Gram positive and Gram negative bacteria and compound N-(2-methyl-5-nitrophenyl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl] benzamide showed excellent antifungal potential against Candida albicans and Aspergillus niger. The computational studies were also executed to predict the drug-likeness and ADMET properties of the title compounds. The N-(alkyl/aryl)-2-chloro-4-nitro-5-[(4-nitrophenyl)sulfamoyl]benzamide derivatives showed significant antidiabetic and antimicrobial potential which is equally supported by the molecular dynamic and docking studies. This study will prove useful in revealing the molecular structure and receptor target site details which can be further utilized for the development of newer active antidiabetic and antimicrobial agents.