In Silico Study of Aglycon Curculigoside A and Its Derivatives as α-Amilase Inhibitors

Nursamsiar, Nursamsiar; Mangande, Maya M.; Awaluddin, Akbar; Nur, Syamsu; Asnawi, Aiyi

doi:10.24198/ijpst.v7i1.23062

Cited by 16 publications

(17 citation statements)

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“…Visualization of docking poses and interacting were carried out by using the Discovery Studio Visualizer [24]. Preparation of macromolecule and ligands, as well as docking studies, were carried out using AutoDock 4.2 [25][26][27] and exploring ligand stability in protein crystal structures was carried out using Amber18 [28].…”

Section: Hardware and Softwarementioning

confidence: 99%

Molecular Docking and Molecular Dynamics Studies of Acalypha Indica L. Phytochemical Constituents With Caspase-3

et al. 2021

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Objective: This study investigated the structure-based molecular interactions between phytochemical constituents of Acalypha indica L. and caspase-3. Methods: Thirty-three phytochemical constituents of A. indica were screened against caspase-3. The X-ray crystal structure of human caspase-3 was retrieved from https://www.rcsb.org/structure/. The molecular interactions of the phytochemicals were studied using the AutoDock 4.2 software and followed by molecular dynamics (MD) simulations using the Amber18 software. Results: From this study, 25 screened phytochemicals were found to have a better binding mode than the native ligand. Moreover, the binding stability of the top four hits evaluated by MD indicated that the hydrogen bonds in MD were quite different from the molecular docking results due to the massive receptor and ligand movement in the MD simulations. However, with the exception of stigmasterol, all ligands were able to stabilize the protein. Conclusion: This study suggested that γ-sitosterol acetate, β-sitosterol acetate, and γ-sitosterol might be able to induce caspase-3, thereby activating apoptosis. These high-affinity compounds can bind to caspase-3 more efficiently and were able to stabilize the protein. Therefore, they have the potential to be used as lead compounds in the treatment of cancer.

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Section: Hardware and Softwarementioning

confidence: 99%

Molecular Docking and Molecular Dynamics Studies of Acalypha Indica L. Phytochemical Constituents With Caspase-3

et al. 2021

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“…Nakamura and group had also observed the interactions of Asp203, Asp327, and Asp542 residues with the salacinol and its derivatives during in silico screening against α-glucosidase enzyme [ 35 ]. Similarly, the aglycone of curculigoside A, and derivatives, blocked the activity of α-glucosidase enzyme via bindings with Asp203, Asp327, and Asp542 residues [ 36 ]. In silico analysis of anthocyanidins and anthocyanins proved them good inhibitors of the α-glucosidase enzyme.…”

Section: Resultsmentioning

confidence: 99%

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

et al. 2021

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α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by 1H-NMR, 13C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC50 value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC50 value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC50 = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.

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“…These compounds also showed their inhibitory action by interacting with the selected residues, Asp203, Asp327, and Asp542 [61]. Similarly, aglycone of curculigoside A and its derivatives also exhibited good in silico inhibition of α-glucosidase enzymes via interactions with Asp203, Asp327, and Asp542 residues [62]. The ligands 12a, 12d, 12e, and 12g having docking scores from −13.47 to −14.23 Kcal/mol were ranked the most effective antidiabetic scaffolds.…”

Section: Molecular Docking (In Silico Analysis)mentioning

confidence: 93%

Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach

et al. 2021

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Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.

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In Silico Study of Aglycon Curculigoside A and Its Derivatives as α-Amilase Inhibitors

Cited by 16 publications

References 0 publications

Molecular Docking and Molecular Dynamics Studies of Acalypha Indica L. Phytochemical Constituents With Caspase-3

Molecular Docking and Molecular Dynamics Studies of Acalypha Indica L. Phytochemical Constituents With Caspase-3

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach

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