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Alpha-Glucosidase Inhibitory and Hypoglycemic Effects of Imidazole-Bearing Thioquinoline Derivatives With Different Substituents: In Silico, in Vitro, and in Vivo Evaluations Publisher Pubmed



Azmi A1 ; Noori M2, 3 ; Khalili Ghomi M3 ; Nazari Montazer M3 ; Iraji A4, 5 ; Dastyafteh N2, 3 ; Oliyaei N10 ; Khoramjouy M1 ; Rezaei Z6 ; Javanshir S2 ; Mojtabavi S7 ; Faramarzi MA7 ; Asadi M8 ; Faizi M9 Show All Authors
Authors
  1. Azmi A1
  2. Noori M2, 3
  3. Khalili Ghomi M3
  4. Nazari Montazer M3
  5. Iraji A4, 5
  6. Dastyafteh N2, 3
  7. Oliyaei N10
  8. Khoramjouy M1
  9. Rezaei Z6
  10. Javanshir S2
  11. Mojtabavi S7
  12. Faramarzi MA7
  13. Asadi M8
  14. Faizi M9
  15. Mahdavi M3
Show Affiliations
Authors Affiliations
  1. 1. Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Pharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  6. 6. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Science, Tehran, Iran
  9. 9. Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  10. 10. Department of Food Science and Technology, School of Agriculture Shiraz University, Shiraz, Iran

Source: Bioorganic Chemistry Published:2024


Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with Ki = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health. © 2024
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