A new route to the synthesis of 2-hydrazolyl-4-thiazolidinone hybrids, evaluation of α-glucosidase inhibitory activity and molecular modeling insights
Saghi Sepehri,
Ghazaleh Farhadi,
Maryam Maghbul,
Farough Nasiri,
Mohammad Ali Faramarzi,
Karim Mahnam,
Somayeh Mojtabavi,
Mohammad Mahdavi,
Zhaleh Moharrami Oranj
Affiliations
Saghi Sepehri
Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran; Corresponding author. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Ghazaleh Farhadi
Students Research Committee, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
Maryam Maghbul
Department of Applied Chemistry, University of Mohaghegh Ardabili, Ardabil, Iran
Farough Nasiri
Department of Applied Chemistry, University of Mohaghegh Ardabili, Ardabil, Iran; Corresponding author.
Mohammad Ali Faramarzi
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Karim Mahnam
Department of Biology, Faculty of Sciences, Shahrekord University, Shahrekord, Iran
Somayeh Mojtabavi
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Mahdavi
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Corresponding author.
Zhaleh Moharrami Oranj
Department of Applied Chemistry, University of Mohaghegh Ardabili, Ardabil, Iran
One of the multifactorial worldwide health syndromes is diabetes mellitus which is increasing at a disturbing rate. The inhibition of α-glucosidase, an enzyme that catalyzes starch hydrolysis in the intestine, is one helpful therapeutic approach for controlling hyperglycemia related to type-2 diabetes. To discover α-glucosidase inhibitors, some 2-hydrazolyl-4-thiazolidinone hybrids (3a-e) were synthesized from new one-pot reaction procedures. Next, their chemical structures were confirmed by 1H NMR, 13C NMR, and FT-IR spectra, and elemental analysis technique. Then, the α-glucosidase inhibitory activity of the titled compounds was evaluated. Among them, derivatives 3b and 3c revealed the highest activity against α-glucosidase compared to acarbose as a drug. Enzyme kinetic studies of the most active derivative (3b) indicated a competitive inhibition. Finally, molecular modeling studies were accomplished to describe vital interactions of the most potent compounds (3b and 3c) with the α-glucosidase enzyme.
