| Autor: |
Moghadam ES; Drug Design & Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran., Al-Sadi AM; Department of Crop Sciences, College of Agricultural & Marine Sciences, Sultan Qaboos University, PO Box 34, Al-Khod 123, Muscat, Sultanate of Oman., Moghadam MS; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran., Bayati B; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran., Mojtabavi S; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Faramarzi MA; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Amini M; Drug Design & Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran., Abdel-Jalil R; Department of Chemistry, College of Science, Sultan Qaboos University, PO Box 36, Al-Khod 123, Muscat, Sultanate of Oman. |
| Abstrakt: |
Background: Diabetes is characterized by a lack of insulin and insensitivity to insulin. In 2013, the global diabetes population was 382 million, with 90% of them having type 2 diabetes (non-insulin-dependent). It is predicted that this number will increase to 592 million by 2035. Aim: Here, we aimed to synthesize a series of benzimidazole-based derivatives B1 - B32 with α-glucosidase inhibition potential as antidiabetic agents. Methods: Compounds B1 - B32 were prepared in three three-step reactions, and the structures were elucidated using spectroscopic methods, namely 1H NMR, 13C NMR, MS and IR. Enzyme inhibition and kinetic study were done using commercial assay kits, and molecular docking study using autodock4. Results: Bioassay data showed that twenty-four out of the thirty-two tested compounds exhibited IC50 values ranging from 44 to 745 μM, surpassing the standard molecule, acarbose (IC50: 750 μM). it was determined that the best compound, B10 , functions as a competitive inhibitor. Additionally, a molecular docking study provided insights into the interactions between the four most promising compounds ( B5 , B6 , B10 and B28 ) and the active site residues within the enzyme. Conclusion: The tested compounds are interesting α-glucosidase inhibitors, which indicates the benefit of more bioassay studies, especially in vivo studies. |
