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Discovery of Novel 4,5-Diphenyl-Imidazol-Α-Aminophosphonate Hybrids As Promising Anti-Diabetic Agents: Design, Synthesis, in Vitro, and in Silico Enzymatic Studies Publisher Pubmed



Zareei S1 ; Ranjbar S2, 3 ; Mohammadi M4 ; Ghasemi Y2, 3 ; Golestanian S4 ; Avizheh L5 ; Moazzam A5 ; Larijani B5 ; Mohammadikhanaposhtani M6 ; Tarahomi MM7 ; Mahdavi M5 ; Sadeghian N8 ; Taslimi P8
Authors
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Authors Affiliations
  1. 1. School of Chemistry, Alborz Campus, University of Tehran, Tehran, 14155-6619, Iran
  2. 2. Computational Vaccine and Drug Design Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  4. 4. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  7. 7. CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran
  8. 8. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey

Source: Bioorganic Chemistry Published:2023


Abstract

Herein, a novel series of 4,5-diphenyl-imidazol-α-aminophosphonate hybrids 4a-m was designed, synthesized, and evaluated as new anti-diabetic agents. These compounds were evaluated against two important target enzymes in the diabetes treatment: α-glucosidase and α-amylase. These new compounds were synthesized in three steps and characterized by different spectroscopic techniques. The in vitro evaluations demonstrated that all the synthesized compounds 4a-m were more potent that standard inhibitor acarbose against studied enzymes. Among these compound, the most potent compound against both studied enzymes was 3-bromo derivative 4l. The latter compound with IC50 = 5.96 nM was 18-times more potent than acarbose (IC50 = 106.63 nM) against α-glucosidase. Moreover, compound 4l with IC50 = 1.62 nM was 27-times more potent than acarbose (IC50 = 44.16 nM) against α-amylase. Molecular docking analysis revealed that this compound well accommodated in the binding site of α-glucosidase and α-amylase enzymes with notably more favorable binding energy as compared to acarbose. © 2023 Elsevier Inc.
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