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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

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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