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2000
Volume 22, Issue 6
  • ISSN: 1570-1794
  • E-ISSN: 1875-6271

Abstract

Background

α-Glucosidase inhibitors play an important role in the treatment of type 2 diabetes mellitus. Inhibitors of the latter enzyme that are available on the market created gastrointestinal side effects and achieve to a high potent and low side effect potent α-glucosidase inhibitors is a valuable target for medicinal chemists.

Objectives

In this study, derivatives of benzimidazole-phenoxy-1,2,3-triazole-benzyl skeleton were introduced as new α-glucosidase inhibitors.

Methods

Twelve derivatives of target scaffold were synthesized simple chemical reactions with a yield between 65 and 88%. The α-glucosidase inhibition activities of these compounds was evaluated against yeast form of this enzyme. After the determination of most potent compound, the interaction of this compound with α-glucosidase was evaluated by kinetic study and by docking study. Drug-likeness, pharmacokinetics, and toxicity profiles of the most potent compound were predicted by an online software.

Results

Anti-α-glucosidase assay demonstrated that all synthesized derivatives were more potent that standard inhibitor acarbose. Representatively, 2-(4-((1-benzyl-1-1,2,3-triazol-4-yl)methoxy)phenyl)-1-benzo[d]imidazole (compound ) as the most potent derivative was 150-times more potent than positive control. Kinetic study of compound revealed that this compound is an uncompetitive inhibitor against α-glucosidase. Furthermore, molecular docking study showed that compound with favorable binding energy attached to important residues in the α-glucosidase active site. This compound also can be an oral drug with favorable toxicity profile.

Conclusion

Benzimidazole-phenoxy-1,2,3-triazole-benzyl derivatives synthesized and evaluated for anti-α-glucosidase activity. All these compounds were excellent α-glucosidase inhibitor, and compound demonstrated the most significant inhibition effect when compared with positive control.

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2025-10-16

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Benzimidazole-phenoxy-1,2,3-triazole-benzyl Derivatives as the New Potent α-glucosidase Inhibitors: Design, Synthesis, In Vitro, and In Silico Biological Evaluations
Curr. Org. Synth. 22, 721 (2025); https://doi.org/10.2174/0115701794335556241209175911
/content/journals/cos/10.2174/0115701794335556241209175911
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  • Article Type:     Research Article
Keyword(s): 1,2,3-triazole; Diabetes mellitus; docking; pharmacokinetics; toxicity; α-glucosidase

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