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Oxamide Derivatives as Potent α ‐Glucosidase Inhibitors: Design, Synthesis, In Vitro Inhibitory Screening and In Silico Docking Studies
Author(s) -
Malik Naseema Perveen,
Naz Maira,
Ashiq Uzma,
Jamal Rifat A.,
Gul Sana,
Saleem Faiza,
Khan Khalid M.,
Yousuf Sammer
Publication year - 2021
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202101709
Subject(s) - oxamide , docking (animal) , chemistry , in silico , uncompetitive inhibitor , enzyme , inhibitory postsynaptic potential , combinatorial chemistry , stereochemistry , aniline , biochemistry , non competitive inhibition , organic chemistry , medicine , nursing , gene
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 1 H‐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 (IC 50 ranges in between 38.2‐75.8 μ M) when compared with the standard 1‐deoxynojirimycin (DNJ) with IC 50 =425.6±1.3 μ M. 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