In Silico Study of Alkaloids as α-Glucosidase Inhibitors: Hope for the Discovery of Effective Lead Compounds

Zafar, Maryam; Khan, Haroon; Khan, Ajmal; Lodhi, Muhammad Arif

doi:10.3389/fendo.2016.00153

Cited by 26 publications

(17 citation statements)

References 31 publications

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“…Zafar and Khan (2016) recently reported that the alkaloids isolated from some of Campanulaceae and Lobelia species, along with standard acarbose, exert significant anti-glucosidase effects. Strong hydrogen bond binding modes of these inhibitors display four interactions between amino acid side chain and hydrogen bonds (Lys155, Glu304, Arg312, and Asn153) [ 82 ].…”

Section: Polyphenols and Plant Familiesmentioning

confidence: 99%

In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes

Riyaphan¹,

Pham

Leong

et al. 2021

Biomolecules

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Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., Bignoniaceae, Ericaceae, Dryopteridaceae, Campanulaceae, Geraniaceae, Euphorbiaceae, Rubiaceae, Acanthaceae, Rutaceae, and Moraceae as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through Monte Carto molecular modeling. Autodock, MOE-Dock, Biovia Discovery Studio, PyMOL, and Accelrys have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.

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Section: Polyphenols and Plant Familiesmentioning

confidence: 99%

In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes

Riyaphan¹,

Pham

Leong

et al. 2021

Biomolecules

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show abstract

“…Glucose control is an effective and long-lasting treatment for type II diabetes mellitus, minimizing both cardio-vascular and nervous system symptoms associated with the disease [30,31]. α-glucosidase inhibitors are usually recommended for diabetic patients to decrease postprandial hyperglycemia caused by the breakdown of starch molecules in the small intestine [32].…”

Section: Discussionmentioning

confidence: 99%

Molecular Docking of Isolated Alkaloids for Possible α-Glucosidase Inhibition

et al. 2019

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Diabetes mellitus, one of the most common endocrine-metabolic disorders, has caused significant morbidity and mortality worldwide. To avoid sugar digestion and postprandial hyperglycemia, it is necessary to inhibit α-glucosidase, a digestive enzyme with an important role in carbohydrate digestion. The criteria for the selection of alkaloids are based on their in vitro and in vivo activities on glucose modulation. The current study assessed the bonding potential of isolated alkaloids with the targeted protein. For this purpose, the 3D structure of the target protein (α-glucosidase) was reproduced using MODELLER 9.20. The modeled 3D structure was then validated and confirmed by using the RAMPAGE, ERRAT, and Verify3D online servers. The molecular docking of 32 alkaloids reported as α-glucosidase inhibitors, along with reference compounds (acarbose and miglitol), was done through MOE-Dock applied in MOE software to predict the binding modes of these drug-like compounds. The results revealed that nummularine-R and vindoline possess striking interactions with active site residues of the target protein, and were analogous to reference ligands. In conclusion, the current study provided a computational background to the α-glucosidase inhibitors tested. This novel information should facilitate the development of new and effective therapeutic compounds for the treatment of diabetes mellitus.

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“…It differs from α-glucosidase in that it acts on 1,4-bonds. α-Glucosidase is a catalytic enzyme that converts starch and disaccharides into glucose [30]. The process of carbohydrate digestion is slowed when α-glucosidase is inhibited, which helps to avoid postprandial hyperglycemia, which is a primary cause of chronic diabetes and its consequences [31].…”

Section: Binding Interactions Of Luteolin With the α-Glucosidasementioning

confidence: 99%

Luteolin: A Potential Multiple Targeted Drug Effectively Inhibits Diabetes Mellitus Protein Targets

Davella

Mamidala

2021

JPRI

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Background: Diabetes is a significant health problem that has reached worrisome proportions: almost half of the world's population now has diabetes. Diabetes mellitus, or diabetes, is a severe, long-term disease in which a person's blood glucose levels are elevated due to their body's inability to make any or enough insulin, or to properly utilise the insulin that it does produce. The chemicals extracted from medicinal plants were shown to be both safer and more bioactive than manufactured medicines. Objective: The goal of this research was to use molecular docking to find possible binding affinities of luteolin, a phytocompound from Rumex vesicarius L, to five target proteins, in order to find the lead molecule against diabetes. Methodology: One chemical was isolated from Rumex vesicarius L. leaves in this research. The binding affinity of the complexes was calculated using molecular docking studies. The docking procedure was carried out using AutoDock Tools 1.5.6, which brought the ligand together with the target proteins. Results: The binding energies of Luteolin with major Glutamine-fructose-6-phosphate amido transferase (GFAT1), Pancreatic α-Amylase, Forkhead box protein O1(FOX01), α--glucosidase, and Dipeptidyl peptidase-4 (DPP-4) were determined to be -6.89, -6.80, -6.36, -9.35, and -7.72 kcal. Conclusion: Our findings suggest that luteolin can target not only α--glucosidase but also DPP4 and other targets, suggesting that they may be used as type 2 diabetes mellitus inhibitors. We believe that this phytochemical, luteolin, may be utilised in preclinical studies as an anti-diabetic drug to combat diabetes mellitus.

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In Silico Study of Alkaloids as α-Glucosidase Inhibitors: Hope for the Discovery of Effective Lead Compounds

Cited by 26 publications

References 31 publications

In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes

In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes

Molecular Docking of Isolated Alkaloids for Possible α-Glucosidase Inhibition

Luteolin: A Potential Multiple Targeted Drug Effectively Inhibits Diabetes Mellitus Protein Targets

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