Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations

Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations Publisher Pubmed

Soltaninejad A ; Shirzad H ; Panji M ; Motevaseli E ; Mousavinezhad SA ; Kalbasi S

Source: Current Organic Synthesis Published:2025

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 8a-l of target scaffold were synthesized via simple chemical reactions with a yield between 65 and 88%. The in vitro 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 in vitro by kinetic study and in silico 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 8a-l were more potent that standard inhibitor acarbose. Representatively, 2-(4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazole (compound 8a) as the most potent derivative was 150-times more potent than positive control. Kinetic study of compound 8a revealed that this compound is an uncompetitive inhibitor against α-glucosidase. Furthermore, molecular docking study showed that compound 8a 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 8a-l synthesized and evaluated for anti-α-glucosidase activity. All these compounds were excellent α-glucosidase inhibitor, and compound 8a demonstrated the most significant inhibition effect when compared with positive control. © 2025 Elsevier B.V., All rights reserved.

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Style	Citing Format
MLA	Soltaninejad A, et al.. "Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations." Current Organic Synthesis, vol. 22, no. 6, 2025, pp. 721-729.
APA	Soltaninejad A, Shirzad H, Panji M, Motevaseli E, Mousavinezhad SA, Kalbasi S (2025). Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations. Current Organic Synthesis, 22(6), 721-729.
Chicago	Soltaninejad A, Shirzad H, Panji M, Motevaseli E, Mousavinezhad SA, Kalbasi S. "Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations." Current Organic Synthesis 22, no. 6 (2025): 721-729.
Harvard	Soltaninejad A et al. (2025) 'Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations', Current Organic Synthesis, 22(6), pp. 721-729.
Vancouver	Soltaninejad A, Shirzad H, Panji M, Motevaseli E, Mousavinezhad SA, Kalbasi S. Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations. Current Organic Synthesis. 2025;22(6):721-729.
BibTex	@article{ author = {Soltaninejad A and Shirzad H and Panji M and Motevaseli E and Mousavinezhad SA and Kalbasi S}, title = {Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations}, journal = {Current Organic Synthesis}, volume = {22}, number = {6}, pages = {721-729}, year = {2025} }
RIS	TY - JOUR AU - Soltaninejad A AU - Shirzad H AU - Panji M AU - Motevaseli E AU - Mousavinezhad SA AU - Kalbasi S TI - Benzimidazole-Phenoxy-1,2,3-Triazole-Benzyl Derivatives As the New Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations JO - Current Organic Synthesis VL - 22 IS - 6 SP - 721 EP - 729 PY - 2025 ER -

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