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Design of new α-glucosidase inhibitors based on the bis-4-hydroxycoumarin skeleton: Synthesis, evaluation, and in silico studies.

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.

SUBMITTER: Soleimani Z 

PROVIDER: S-EPMC11319329 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Design of new α-glucosidase inhibitors based on the bis-4-hydroxycoumarin skeleton: Synthesis, evaluation, and in silico studies.

Soleimani Zahra Z   Mohammadi Mohammad M   Halimi Mohammad M   Safapoor Sajedeh S   Dastyafteh Navid N   Safaie Elham E   Mojtabavi Somayeh S   Faramarzi Mohammad Ali MA   Bozorgi-Koushalshahi Maryam M   Larijani Bagher B   Mohammadi-Khanaposhtani Maryam M   Mahdavi Mohammad M  

Scientific reports 20240812 1

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 (IC<sub>50</sub> values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC<sub>50</sub> = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5  ...[more]

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