Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential α-glucosidase inhibitors

Asemanipoor, Nafise; Mohammadi‐Khanaposhtani, Maryam; Moradi, Sajad; Vahidi, Mahbobeh; Asadi, Mehdi; Faramarzi, Mohammad Ali; Mahdavi, Mohammad; Biglar, Mahmood; Larijani, Bagher; Hamedifar, Haleh; Hajimiri, Mir Hamed

doi:10.1016/j.bioorg.2019.103482

Cited by 64 publications

(41 citation statements)

References 15 publications

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“…α‐Glucosidase inhibition assay of acridine‐9‐carboxamide‐1,2,3‐triazoles 7a‐m and kinetic study of most potent compound 7j were performed on yeast α‐glucosidase ( Saccharomyces cerevisiae , EC3.2.1.20, 20 U/mg) according to previous works [18–21] …”

Section: Methodsmentioning

confidence: 99%

“…2.17 | In vitro α-glucosidase inhibition assay and kinetic study α-Glucosidase inhibition assay of acridine-9-carboxamide-1,2,3-triazoles 7a-m and kinetic study of most potent compound 7j were performed on yeast α-glucosidase (Saccharomyces cerevisiae, EC3.2.1.20, 20 U/mg) according to previous works. [18][19][20][21] 2.18 | Docking study For docking study, since Saccharomyces cerevisiae form of α-glucosidase has not any crystallographic structure in protein data bank (PDB), homology model of it was constructed by using SWISS-MODEL Repository according to our previous paper. [19]…”

Section: General Chemistrymentioning

confidence: 99%

“…Then, these compounds evaluated against yeast α-glucosidase by in vitro and in silico assays. [19][20][21] As acridine is found in numerous anti-tumor agents, cytotoxic effects of title compounds were evaluated against cancer and normal human cells by MTT assay. [22] 2 | EXPERIMENTAL…”

Section: Introductionmentioning

confidence: 99%

“…Thus, in continuation of our attempts for design and synthesis of new heterocyclic compounds as potent α‐glucosidase inhibitors, herein, we designed a new series of acridine‐9‐carboxamide‐1,2,3‐triazoles 7a‐m and synthesized them with simple reactions. Then, these compounds evaluated against yeast α‐glucosidase by in vitro and in silico assays [19–21] . As acridine is found in numerous anti‐tumor agents, cytotoxic effects of title compounds were evaluated against cancer and normal human cells by MTT assay [22]…”

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, biological evaluation, and docking study of new acridine‐9‐carboxamide linked to 1,2,3‐triazole derivatives as antidiabetic agents targeting α‐glucosidase

Asgari

Tahmasebi

Mojtabavi

et al. 2020

Journal of Heterocyclic Chem

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A new series of acridine-9-carboxamide-1,2,3-triazole derivatives 7a-m were designed, synthesized, and evaluated as novel α-glucosidase inhibitors. Acridine-9-carboxamide-1,2,3-triazole scaffold has been designed by combination of effective moieties from potent α-glucosidase inhibitors. Most of the synthesized compounds were more potent than standard inhibitor acarbose. Among the title compounds, the most potent compounds were compounds 7j, 7k, and 7a with IC 50 values of 120.2 ± 1.0, 151.1 ± 1.4, and 157.6 ± 1.6 μM, respectively (IC 50 value of acarbose = 750.0 ± 10.0 μM). Docking study of the most potent compounds demonstrated that these compounds formed stable complexes with α-glucosidase active site. Anti-α-amylase assay of compounds 7j, 7k, and 7a was performed and no activity was observed. in vitro cytotoxicity assay of the latter compounds revealed that these compounds were not cytotoxic toward human normal (HDF) and cancer (MCF-7) cell lines. ADME and toxicity prediction of compounds 7j, 7k, and 7a were also performed.

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Section: Methodsmentioning

confidence: 99%

Section: General Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Design, synthesis, biological evaluation, and docking study of new acridine‐9‐carboxamide linked to 1,2,3‐triazole derivatives as antidiabetic agents targeting α‐glucosidase

Asgari

Tahmasebi

Mojtabavi

et al. 2020

Journal of Heterocyclic Chem

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“…Therefore, the pyrazole ring with two attached phenyl groups was incorporated in the design to provide favorable hydrophobic interactions. Hence, prompted by above observations and in continuation to our attempt in development of α-glucosidase inhibitors, we designed the skeleton of biphenyl pyrazole-benzofuran and evaluation their α-glucosidase inhibition potential [30][31][32][33][34] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of novel pyrazole-benzofuran hybrids: in vitro α-glucosidase inhibitory activity, kinetic and molecular modeling study

Azimi¹,

Azizian²,

Najafi

et al. 2021

Preprint

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In this work, new derivatives of biphenyl pyrazole-benzofuran hybrids designed, synthesized and evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase activity. Newly identified inhibitors were found to be four to eighteen folds more active with IC50 values in the range of 40.6 ± 0.2–164.3 ± 1.8 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 10.0 µM). Limited Structure-activity relationship was established. A kinetic binding study indicated that most active compound 8e acted as the competitive inhibitors of α-glucosidase with Ki = 38 µM. Molecular docking has also been performed to find the interaction modes responsible for the desired inhibitory activity. As expected, all pharmacophoric features used in the design of the hybrid, are involved in the interaction with the active site of the enzyme. In addition, molecular dynamic simulations showed compound 8e oriented vertically into the active site from mouth to the bottom and stabilized the enzyme domains by interacting with the interface of domain A and domain B and the back side of the active site while acarbose formed non-binding interaction with the residue belong to the domain A of the enzyme.

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New phenylthiosemicarbazide‐phenoxy‐1,2,3‐triazole‐N‐phenylacetamides as dual inhibitors against α‐glucosidase and PTP‐1B for the treatment of type 2 diabetes

Ansariashlaghi,

Fakhrioliaei,

Mohammadi‐Khanaposhtani

et al. 2024

Archiv der Pharmazie

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This study describes the design, synthesis, and evaluation of a novel series of phenylthiosemicarbazide‐phenoxy‐1,2,3‐triazole‐N‐phenylacetamide derivatives (7a–l) as dual inhibitors of α‐glucosidase and protein tyrosine phosphatase 1‐B (PTB‐1B). The latter enzymes are two important targets in the treatment of type 2 diabetes. The in vitro obtained data demonstrated that all title compounds 7a–l were more potent than the standard inhibitor acarbose against α‐glucosidase while only four derivatives (7a, 7g, 7h, and 7h) were more potent than the standard inhibitor suramin against PTP‐1B. Furthermore, these data showed that the most potent α‐glucosidase inhibitor was compound 7i, with sixfold higher inhibitory activity than acarbose, and the most potent PTP‐1B inhibitor was compound 7a with 3.5‐fold higher inhibitory activity than suramin. Kinetic studies of compounds 7i and 7a revealed that they inhibited their target enzymes in a competitive mode. The docking study demonstrated that compounds 7i and 7a well occupied the active site pockets of α‐glucosidase and PTP‐1B, respectively. In silico pharmacokinetic and toxicity assays of the most potent compounds were performed, and the obtained results were compared with those of the standard inhibitors.

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Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential α-glucosidase inhibitors

Cited by 64 publications

References 15 publications

Design, synthesis, biological evaluation, and docking study of new acridine‐9‐carboxamide linked to 1,2,3‐triazole derivatives as antidiabetic agents targeting α‐glucosidase

Design, synthesis, biological evaluation, and docking study of new acridine‐9‐carboxamide linked to 1,2,3‐triazole derivatives as antidiabetic agents targeting α‐glucosidase

Design and synthesis of novel pyrazole-benzofuran hybrids: in vitro α-glucosidase inhibitory activity, kinetic and molecular modeling study

New phenylthiosemicarbazide‐phenoxy‐1,2,3‐triazole‐N‐phenylacetamides as dual inhibitors against α‐glucosidase and PTP‐1B for the treatment of type 2 diabetes

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