Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Design of New Α-Glucosidase Inhibitors Based on the Bis-4-Hydroxycoumarin Skeleton: Synthesis, Evaluation, and in Silico Studies Publisher Pubmed

Summary: Can a molecule manage diabetes? A study found a coumarin-triazole compound is 125 times better than standard drugs at controlling blood sugar. #DiabetesResearch #DrugDevelopment

Soleimani Z1 ; Mohammadi M2 ; Halimi M3 ; Safapoor S1 ; Dastyafteh N1 ; Safaie E1 ; Mojtabavi S4 ; Faramarzi MA4 ; Bozorgikoushalshahi M1 ; Larijani B1 ; Mohammadikhanaposhtani M5 ; Mahdavi M1
Authors

Source: Scientific Reports Published:2024


Abstract

In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure–activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose. © The Author(s) 2024.
Other Related Docs