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

Abstract

Diabetes 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

The Effect of Branched Alkyl Chain Length on the Properties of Supramolecular Organogels from Mono-N-Alkylated Primary Oxalamides

“…Given that many oxalamide compounds are biologically and pharmaceutically active [34][35][36][37][38][39][40][41][42][43][44][45], their effect on the metabolic activity of mammalian cells was evaluated. The effect of these compounds on the metabolism of bone marrow-derived mast cells (BMMCs) was evaluated using the XTT assay which measures the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent bioreductase activity of live cells, a key mitochondrial process necessary for energy generation.…”

“…Oxalamide compounds are of considerable interest due to their potential in biomedical applications [34][35][36][37][38][39][40][41][42][43][44][45], catalysis [46][47][48], foods [49], and self-assembling behavior to form gels [50][51][52][53][54][55][56]. The oxalamide functional group consists of two amide groups next to each other in reverse mode, connected by two consecutive carbonyl groups, which has been extensively used as supramolecular synthon to generate LMWGs [50][51][52][53][54][55][56][57][58].…”

Design, Synthesis, In vitro and In silico Alpha Glucosidase and Lipoxygenase Inhibition Studies of Copper(II) Oxamide Complexes

“…Nine out of twenty compounds were found to exhibit strong inhibition potential in the range of IC 50 = 38.2-75.8 μM. [29]…”

“…Oxamides O1-O20 were scanned against α-glucosidase enzyme and the resultant data is already reported by our group previously. [29] DNJ (1-deoxynojirimycin) was used as a standard inhibitor. The inhibitory study showed that all tested compounds exhibited modest inhibition potential (IC 50 ranges in between 38.2-390.8 μM) with standard DNJ (IC 50 = 425.6 � 1.3 μM).…”

“…[28] In addition to this, previously our research group has reported in vitro inhibitory screening and in silico docking studies of oxamide derivatives as potent αglucosidase inhibitors. [29] Combining the unique properties of Cu(II) complexes with the multifaceted characteristics of oxamides opens up intriguing possibilities for the development of novel therapeutic agents.…”