A simple and efficient synthesis of novel inhibitors of alpha-glucosidase based on benzimidazole skeleton and molecular docking studies

Özil, Musa; Emirik, Mustafa; Etlik, Semiha Yılmaz; Ülker, Serdar; Kahveci, Bahittin

doi:10.1016/j.bioorg.2016.08.011

Cited by 48 publications

(28 citation statements)

References 34 publications

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“…Studieso nt he modification of benzimidazoles indicate that electron-donating groups at the N1 position and electron-withdrawingg roups on the imidazole ring are crucial to inhibitory activity.D ocking studies showt hat compound 61 bonds to aglucosidase by forming ahydrogen bond through the carbonyl group and through some other interactions involving p-p stacking interactions. [34] Amonga nother series of 5-bromo-2-arylbenzimidazole derivatives, compound 64 with a4 '-hydroxy group at the C2 position exhibit inhibitory activity that is fivefold higher than that of the standard acarbose (IC 50 = 38.25 mm). [34] Amonga nother series of 5-bromo-2-arylbenzimidazole derivatives, compound 64 with a4 '-hydroxy group at the C2 position exhibit inhibitory activity that is fivefold higher than that of the standard acarbose (IC 50 = 38.25 mm).…”

Section: Other Compoundsmentioning

confidence: 99%

Recent Advances in Synthetic α‐Glucosidase Inhibitors

Liu

2017

ChemMedChem

111

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Over the past few years, the number of people diagnosed with type 2 diabetes has increased owing to an unhealthy diet, a limited amount of exercise, and obesity. The search for novel and efficient antidiabetes agents has become an urgent task for scientists. Among the antidiabetes drugs, α-glucosidase inhibitor drugs have been proven to have many advantages over other drugs, and therefore, a large number of new compounds as α-glucosidase inhibitors has recently been reported. In this review, we summarize these newly found α-glucosidase inhibitors and their structure-activity relationships in antidiabetic studies and provide better structures for α-glucosidase inhibitors or even preclinical candidates. Beyond that, some enlightening strategies for the synthesis of relevant compounds are highlighted.

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Section: Other Compoundsmentioning

confidence: 99%

Recent Advances in Synthetic α‐Glucosidase Inhibitors

Liu

2017

ChemMedChem

111

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“…Due to the sugar-based structure of mentioned α-glucosidase inhibitors, their synthesis needs complicated multistep procedures 6 . Unfortunately, administration of these inhibitors is associated with undesirable side effects including diarrhea, abdominal discomfort, and atulence 7,8 . Thus, it would be essential to develop novel, safe, and e cient α-glucosidase inhibitors as an effective lead candidate for future antidiabetic drug discovery initiatives.…”

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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“…For example, several pyrimidine derivatives have shown excellent inhibition potency [25][26][27][28] . Moreover, compounds containing benzimidazole have become an emerging anti-diabetic scaffold during recent years [29][30][31][32][33][34] . Although there are several reports concerning α-glucosidase inhibitors having benzimidazole and pyrimidine skeletons separately, compounds bearing both of these heterocycles, benzo [4,5]imidazo [1,2-a]pyrimidine, in particular, as anti-diabetic agents have not been proposed yet ( gure 1).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Docking, and Kinetic Study of 3-Amino-2,4-Diarylbenzo[4,5]Imidazo[1,2-a]Pyrimidines as Novel, Potent Α-Glucosidase Inhibitor

Peytam

Takalloobanafshi

Saadattalab

et al. 2021

Preprint

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In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a-ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their α-glucosidase inhibitory activities were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which may provide new drug candidates in the treatment of type II diabetes mellitus. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against α-glucosidase (IC50 = 16.4 ± 0.36 μM) which was 45.7 times more potent than acarbose as standard inhibitor (IC50 = 750.0 ± 1.5 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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A simple and efficient synthesis of novel inhibitors of alpha-glucosidase based on benzimidazole skeleton and molecular docking studies

Cited by 48 publications

References 34 publications

Recent Advances in Synthetic α‐Glucosidase Inhibitors

Recent Advances in Synthetic α‐Glucosidase Inhibitors

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

Design, Synthesis, Molecular Docking, and Kinetic Study of 3-Amino-2,4-Diarylbenzo[4,5]Imidazo[1,2-a]Pyrimidines as Novel, Potent Α-Glucosidase Inhibitor

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