Design, synthesis, and in silico studies of benzimidazole bearing phenoxyacetamide derivatives as α-glucosidase and α-amylase inhibitors

Shayegan, Nahal; Iraji, Aida; Bakhshi, Nasim; Moazzam, Ali; Faramarzi, Mohammad Ali; Mojtabavi, Somayeh; Pour, Seyyed Mehrdad Mostafavi; Tehrani, Maliheh Barazandeh; Larijani, Bagher; Rezaei, Zahra; Yousefi, Pardis; Khoshneviszadeh, Mehdi; Mahdavi, Mohammad

doi:10.1016/j.molstruc.2022.133650

Cited by 16 publications

(7 citation statements)

References 32 publications

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“…The mode of inhibition of the most active compounds 6l and 6m identified with the lowest IC 50 , was investigated against an α-glucosidase activity with different concentrations of p -nitrophenyl α - d -glucopyranoside (1–12 mM) as substrate in the absence and presence of 6l and 6m at different concentrations. A Lineweaver–Burk plot was generated to identify the type of inhibition and the Michaelis–Menten constant ( K m ) value was determined from the plot between the reciprocal of the substrate concentration (1/[S]) and reciprocal of enzyme rate (1/V) over various inhibitors concentrations 30 , 31 .…”

Section: Methodsmentioning

confidence: 99%

Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

Shayegan

Haghipour

Tanideh

et al. 2023

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In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a–o was carried out using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a–o exhibited good α-glucosidase inhibition with IC50 values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC50 = 752.0 ± 2.0 µM). Structure–activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations.

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Section: Methodsmentioning

confidence: 99%

Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

Shayegan

Haghipour

Tanideh

et al. 2023

Sci Rep

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“…Ligands were prepared by OPLS_2005 force field using EPIK. The grid box was generated for each binding site using entries with a box size of 25 A, the derivative was docked on binding sites using induced-fit docking, reporting 10 poses per ligand to form the final complex [ 14 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…As a consequence, novel inhibitors are required to improve DM treatment. Numerous studies have described the inhibition of α-glucosidase induced by triazole [ 12 ], chromene [ 12 ], pyridine [ 13 ], quinolone [ 3 ], cyanoacetohydrazide [ 7 ], and benzimidazole [ 14 ] based compounds.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and bioactivities evaluation of quinazolin-4(3H)-one derivatives as α-glucosidase inhibitors

et al. 2022

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The development of new antidiabetes agents is necessary to obtain optimal glycemic control and overcome its complications. Different quinazolin-4(3H)-one bearing phenoxy-acetamide derivatives (7a–r) were designed and synthesized to develop α-glucosidase inhibitors. All the synthesized derivatives were evaluated against α-glucosidase in vitro and among them, compound 7b showed the highest α-glucosidase inhibition with an IC50 of 14.4 µM, which was ∼53 times stronger than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compound 7b was a competitive type towards α-glucosidase. Also, molecular docking studies analyzed the interaction between the most potent derivative and α-glucosidase. Current findings indicate the new potential of quinazolin-4(3H)-ones that could be used for the development of novel agents against diabetes mellitus.

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“…1. 20–26 However, a majority of them lack the prerequisite of an undiscriminating drug candidate and warrant a search for a new category of α-amylase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Development of thiazole-appended novel hydrazones as a new class of α-amylase inhibitors with anticancer assets: an in silico and in vitro approach

et al. 2023

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Design, synthesis, and in silico studies of benzimidazole bearing phenoxyacetamide derivatives as α-glucosidase and α-amylase inhibitors

Cited by 16 publications

References 32 publications

Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

Synthesis and bioactivities evaluation of quinazolin-4(3H)-one derivatives as α-glucosidase inhibitors

Development of thiazole-appended novel hydrazones as a new class of α-amylase inhibitors with anticancer assets: an in silico and in vitro approach

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