Synthesis, in-vitro evaluation, molecular docking, and kinetic studies of pyridazine-triazole hybrid system as novel α-glucosidase inhibitors
| Autor: | Loghman Firoozpour, Fatemeh Madani-Qamsari, Roya Pakrad, Somayeh Mojtabavi, Somayeh Salarinejad, Mohammad Ali Faramarzi, Mahsa Toolabi, Saeed Karima, Fatemeh Safari, Setareh Moghimi, Seyed Esmaeil Sadat Ebrahimi, Alireza Foroumadi |
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| Rok vydání: | 2021 |
| Předmět: |
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Molecular Protein Conformation Stereochemistry Triazole Saccharomyces cerevisiae 01 natural sciences Biochemistry Cell Line Pyridazine Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Humans Glycoside Hydrolase Inhibitors Molecular Biology Acarbose chemistry.chemical_classification Binding Sites Molecular Structure 010405 organic chemistry Organic Chemistry alpha-Glucosidases Triazoles In vitro Yeast 0104 chemical sciences Pyridazines 010404 medicinal & biomolecular chemistry Enzyme chemistry Docking (molecular) Drug Design Click chemistry Protein Binding medicine.drug |
| Zdroj: | Bioorganic Chemistry. 109:104670 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2021.104670 |
| Popis: | 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 IC50 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. |
| Databáze: | OpenAIRE |
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