Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a–5v) has been synthesized and confirmed by physicochemical(Rf, melting point) and spectral means (IR, 1HNMR, 13CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH3-5-NO2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH3) group and electron withdrawing (NO2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski’s rule of 5 and Veber’s rule.[graphic not available: see fulltext]