1. Synthesis, in-vitro evaluation, molecular docking, and kinetic studies of pyridazine-triazole hybrid system as novel α-glucosidase inhibitors.
- Author
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Moghimi S, Salarinejad S, Toolabi M, Firoozpour L, Esmaeil Sadat Ebrahimi S, Safari F, Madani-Qamsari F, Mojtabavi S, Faramarzi MA, Karima S, Pakrad R, and Foroumadi A
- Subjects
- Binding Sites, Cell Line, Drug Design, Glycoside Hydrolase Inhibitors chemistry, Humans, Models, Molecular, Molecular Structure, Protein Binding, Protein Conformation, Pyridazines chemistry, Saccharomyces cerevisiae enzymology, Structure-Activity Relationship, Triazoles chemistry, alpha-Glucosidases metabolism, Pyridazines pharmacology, Triazoles pharmacology
- Abstract
In this study, we reported the discovery of pyridazine based 1,2,3-triazole derivatives as inhibitors of α-glucosidase. All target compounds exhibited significant inhibitory activities against yeast and rat α-glucosidase enzymes compared to positive control, acarbose. The most potent compound 6j, ethyl 3-(2-(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)ethyl)-5,6-diphenylpyridazine-4-carboxylate exhibited IC
50 values of 58, and 73 µM. Docking studies indicated the responsibility of hydrophobic and hydrogen bonding interactions in the ligand-enzyme complex stability. The in-vitro safety against the normal cell line was observed by toxicity evaluation of the selected compounds., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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