Synthesis, molecular docking studies of hybrid benzimidazole as α -glucosidase inhibitor

Zawawi, Nik Khairunissa Nik Abdullah; Taha, Muhammad; Ahmat, Norizan; Ismail, Nor Hadiani; Wadood, Abdul

doi:10.1016/j.bioorg.2016.12.009

Cited by 49 publications

(12 citation statements)

References 45 publications

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“…According to molecular docking study of the most potent compound ( A, Fig. 1 ), imidazole moiety formed hydrogen bond with Glu 276, and phenyl rings showed arene–arene interaction with residue Phe 157 of the α-glycosidase active site [ 27 ]. In 2019, Taha et al evaluated novel benzimidazole-based oxadiazole derivatives for their in vitro anti-α-glycosidase activity.…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

et al. 2021

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A novel series of phenoxymethybenzoimidazole derivatives ( 9a-n ) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC 50 values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC 50 = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c , 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10310-7.

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Section: Resultsmentioning

confidence: 99%

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

et al. 2021

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“…There are many reports about introducing bromine atoms on the aromatic ring to search a potent α-glucosidase inhibitory. For example, Zawawi and his co-workers [26] found that the position of bromine atoms on the aromatic ring of the inhibitors affected the activity on α-glucosidase. It indicated that electron withdrawing moieties, like NO 2 , the Br and Cl, are more favourable for the interactions with active site residues; Kim et al [27,28,29] reported that the number of Br atoms in a benzene ring may significantly influence the activity of inhibitors.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Activity Evaluation of Novel N-benzyl Deoxynojirimycin Derivatives for Use as α-Glucosidase Inhibitors

et al. 2019

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To obtain α-glucosidase inhibitors with high activity, 19 NB-DNJDs (N-benzyl-deoxynojirimycin derivatives) were designed and synthesized. The results indicated that the 19 NB-DNJDs displayed different inhibitory activities towards α-glucosidase in vitro. Compound 18a (1-(4-hydroxy-3-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol) showed the highest activity, with an IC50 value of 0.207 ± 0.11 mM, followed by 18b (1-(3-bromo-4-hydroxy-5-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol, IC50: 0.276 ± 0.13 mM). Both IC50 values of 18a and 18b were significantly lower than that of acarbose (IC50: 0.353 ± 0.09 mM). According to the structure-activity analysis, substitution of the benzyl and bromine groups on the benzene ring decreased the inhibition activity, while methoxy and hydroxyl group substitution increased the activity, especially with the hydroxyl group substitution. Molecular docking results showed that three hydrogen bonds were formed between compound 18a and amino acids in the active site of α-glucosidase. Additionally, an arene‒arene interaction was also modelled between the phenyl ring of compound 18a and Arg 315. The three hydrogen bonds and the arene‒arene interaction resulted in a low binding energy (–5.8 kcal/mol) and gave 18a a higher inhibition activity. Consequently, compound 18a is a promising candidate as a new α-glucosidase inhibitor for the treatment of type Ⅱ diabetes.

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“…Benzimidazolyl heterocycle is also considered for conjugation with the targeted compounds due to the diverse biological properties exhibited by its derivatives such as antitumor [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , anti-inflammatory [32] , antitubercular [33] , [34] , [35] , anti-HIV (human immunodeficiency virus) [36] , [37] , [38] , α -glucosidase inhibition [39] , [40] , [41] , cholinesterase inhibitor useful to combat the neuromuscular disorders [42] , pancreatic lipase inhibitor useful for fat absorption control [43] , α -amylase inhibitor useful for diabetes, obesity, and oral diseases [44] and Rho-kinase inhibitor useful for treatment of glaucoma [45] . Treanda (Bendamustine hydrochloride) is a benzimidazolyl derivative approved by FDA (2008) for chronic lymphocytic leukemia [46] , [47] .…”

Section: Introductionmentioning

confidence: 99%

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2

Girgis

Panda

Srour

et al. 2021

Bioorganic Chemistry

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Synthesis, molecular docking studies of hybrid benzimidazole as α -glucosidase inhibitor

Cited by 49 publications

References 45 publications

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

Design, Synthesis, and Activity Evaluation of Novel N-benzyl Deoxynojirimycin Derivatives for Use as α-Glucosidase Inhibitors

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2

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