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  3. Discovery of novel 4,5-diphenyl-imidazol-α-aminophosphonate hybrids as promising anti-diabetic agents: Design, synthesis, in vitro, and in silico enzymatic studies

Discovery of novel 4,5-diphenyl-imidazol-α-aminophosphonate hybrids as promising anti-diabetic agents: Design, synthesis, in vitro, and in silico enzymatic studies

  • Bioorg Chem. 2023 Sep 9:141:106846. doi: 10.1016/j.bioorg.2023.106846.
Samira Zareei 1,  Sara Ranjbar 2,  Mohammad Mohammadi 3,  Younes Ghasemi 2,  Sahand Golestanian 3,  Laya Avizheh 4,  Ali Moazzam 4,  Bagher Larijani 4,  Maryam Mohammadi-Khanaposhtani 5,  Mohammad Majid Tarahomi 6,  Mohammad Mahdavi 7,  Nastaran Sadeghian 8,  Parham Taslimi 9
Affiliations

Affiliations

  • 1 School of Chemistry, Alborz Campus, University of Tehran, 14155-6619 Tehran, Iran.
  • 2 Computational Vaccine and Drug Design Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 3 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 4 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 5 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 6 CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.
  • 7 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: momahdavi@tums.ac.ir.
  • 8 Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey.
  • 9 Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey. Electronic address: ptaslimi@bartin.edu.tr.
PMID: 37713948 DOI: 10.1016/j.bioorg.2023.106846
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.

Keywords

4,5-Diphenyl-imidazol; α-Aminophosphonate; α-Amylase; α-Glucosidase.

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