Oxamide Derivatives as Potent α‐Glucosidase Inhibitors: Design, Synthesis, In Vitro Inhibitory Screening and In Silico Docking Studies

Abstract

AbstractDiabetes mellitus (DM) is a well‐known progressive endocrine disorder and has become a serious worldwide medical concern stimulating the search for new therapeutic agents. In the current study, nitrogen and oxygen based twenty oxamide derivatives were synthesized and their potential to inhibit α‐glucosidase enzyme was studied. Oxamides were synthesized using oxalyl chloride and corresponding aniline in 1 : 2 ratio in basic medium. Structures of these compounds were determined by mass spectrometry, various spectroscopic techniques such as 1H‐NMR, and IR spectroscopy as well as X‐ray diffraction studies. Additionally, computational approach was applied for the calculation of vibrational frequencies of oxamide derivatives and both techniques showed comparable results. Good to moderate inhibitory activities were observed for all synthetic derivatives against α‐glucosidase enzyme. Off twenty (20), nine (9) compounds were found to exhibit good inhibitory activities (IC50 ranges in between 38.2‐75.8 μM) when compared with the standard 1‐deoxynojirimycin (DNJ) with IC50=425.6±1.3 μM. Molecular docking studies were performed for the evaluation of binding mechanism of oxamide compounds in the pocket of α‐glucosidase enzyme. Docking scores based on EADock score, inhibitory activities and docking energies showed similar trend of inhibition.Introduction