Virtual Screening of Natural Alpha-Glucosidase Inhibitor from Alpinia Galanga Bioactive Compounds as Anti-Diabetic Candidate (original) (raw)
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Cellular and Molecular Biology
The research aims to identify the inhibitory potential of natural dietary phytochemicals against non-insulinotropic target protein alpha-glucosidase and its possible implications to diabetes mellitus type 2.A data set of sixteen plant-derived dietary molecules viz., 4,5-dimethyl-3-hydroxy-2(5H)-furanone, apigenin, bromelain, caffeic acid, cholecalciferol, dihydrokaempferol 7-o-glucopyranoside, galactomannan, genkwanin, isoimperatorin, luteolin, luteolin 7-o-glucoside, neohesperidin, oleanoic acid, pelargonidin-3-rutinoside, quercetin, and quinic acid were taken to accomplish molecular docking succeeded by their comparison with known inhibitors including acarbose, miglitol, voglibose, emiglitate, and 1-deoxynojirimycin. Among all phyto-compounds, bromelain (ΔG: -9.54 kcal/mol), cholecalciferol (-8.47 kcal/mol), luteolin (-9.02 kcal/mol), and neohesperidin (-8.53 kcal/mol) demonstrated better binding interactions with alpha-glucosidase in comparison to the best-known inhibitor, acarbo...
Recent advances in molecular docking studies using α-glucosidase inhibitors.pdf
Diabetes is a group of metabolic diseases, which is associated with high blood sugar levels. Postprandial hyperglycemia is a primary defect in diabetes which has harmful effects on tiny blood vessels in kidneys, heart, eyes, or nervous system. Diabetes can eventually cause heart disease, blindness, stroke, kidney disease and even nerve damage. One of the effective managements of this disease particularly non-insulin-dependent diabetes mellitus (Type II), is to retard the absorption of glucose by inhibition of carbohydrate hydrolyzing enzyme like alpha-glucosidase, in the digestive organs. An approach for the treatment of this disease is to lower the absorption of glucose in some way in order to obviate the hyperglycemic condition. Plant based medication can also be considered as a good option to treat diabetes. Here we have made a thorough study of the literature in the field of molecular docking of alpha-glucosidase so as to elucidate newer pathways for controlling diabetes type II to some extent. Key Words: Diabetes, alpha- Glucosidase, Phytochemicals, Molecular docking, Inhibitors, QSAR
Journal of Applied Life Sciences International
Diabetes mellitus (DM) is a long term disorder of metabolism characterized by high level of blood sugar (hyperglycemia) due to insufficient secretion of insulin, insulin resistance, or both, as well as poor lipid, protein and carbohydrate metabolism. These complications occur as a result of derangement in glucose storage for the regulatory system and metabolic fuel mobilization, including carbohydrate, protein and lipid anabolism and catabolism emanating from impaired action of insulin, secretion of insulin, or both. The in silico study was conducted with the help of molecular docking to treat diabetes to inhibit the activities of α-amylase and α-glucosidase by drug molecule. All the studies were based on docking with molecules. The docking was done using a docking software between all the ligands and the target protein receptors. Natural compounds, such as Conduritol A, Catechin and Quercetin were picked, and protein targets as α-amylase and α-glucosidase. Ligands were imported for...
Current Issues in Molecular Biology, 2022
Diabetes mellitus is a disorder characterized by higher levels of blood glucose due to impaired insulin mechanisms. Alpha glucosidase is a critical drug target implicated in the mechanisms of diabetes mellitus and its inhibition controls hyperglycemia. Since the existing standard synthetic drugs have therapeutic limitations, it is imperative to identify new potent inhibitors of natural product origin which may slow carbohydrate digestion and absorption via alpha glucosidase. Since plant extracts from Calotropis procera have been extensively used in the treatment of diabetes mellitus, the present study used molecular docking and dynamics simulation techniques to screen its constituents against the receptor alpha glucosidase. Taraxasterol, syriogenin, isorhamnetin-3-O-robinobioside and calotoxin were identified as potential novel lead compounds with plausible binding energies of −40.2, −35.1, −34.3 and −34.3 kJ/mol against alpha glucosidase, respectively. The residues Trp481, Asp518, ...
Molecules (Basel, Switzerland), 2018
Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.
Human pancreatic α-amylase (HPA), which works as a catalyst for carbohydrate hydrolysis, is one of the viable targets to control type 2 diabetes. The inhibition of α-amylase lowers blood glucose levels and helps to alleviate hyperglycemia complications. Herein, we systematically screened the potential HPA inhibitors from an in-house library of natural products by molecular modeling. The modeling encompasses molecular docking, MM/GBSA binding energy calculations, MD simulations, and ADMET analysis. This research identified newboulaside B, newboulaside A, quercetin-3-O-β-glucoside, and sasastilboside A as the top four potential HPA inhibitors from the library of natural products, whose Glide docking scores and MM/GBSA binding energies range from −9.191 to −11.366 kcal/mol and −19.38 to −50.29 kcal/mol, respectively. Based on the simulation, among them, newboulaside B was found as the best HPA inhibitor. Throughout the simulation, with the deviation of 3Å (acarbose = 3Å), it interacted...
Oriental Journal of Chemistry
Most of the biological testing of α-glucosidase inhibitors was carried out on yeast and rat intestinal. The aim of this study was to explore molecular interactions which occurred during inhibition process of human-neutral α-glucosidase by cinnamic acid derivatives. In this paper, cinnamic acid was used as the lead compound whose carboxylic acid moeity was replaced by alkyl amine against the macromolecule target which was human-neutral α-glucosidase enzyme. In order to understand the mechanism of interaction of the ligand binding conformations and to identify potent α-glucosidase inhibitor, molecular modeling studies with homology modeling method were used to investigate the problem. The structure of homology model of human α-glucosidase was built by using neutral-human α-glucosidase (GANC) with 914 amino acid residues from the Swiss-Prot with Q8TET4 identity and using the mold template of 2G3M (PDB ID). The model of enzyme was constructed based on the crystal structure of the S.solphataricus α-glucosidase, Ma1A, and human N-terminal subunit of Maltase Glucoamylase (NtMGAM). The molecular docking simulation of cinnamic acid derivatives was carried out on Autodock 4.2. Two parameters from docking simulation that can predict the inhibition activity of α-glucosidase enzyme are: low free energy Gibs and low kinetic inhibition value. The Gibs free energy value (ΔG) obtained from the docking simulation showed that 13 cinnamic acid derivatives compounds had an affinity for the receptor α-glucosidase. These compound could act as α-glucosidase inhibitor.
Frontiers in Endocrinology, 2016
α-Glucosidase (extinction coefficient 3.2.1.20) is a primary carbohydrate metabolizing enzyme that acts on the 1-4 associated α-glucose residues. The inhibition of α-glucosidase slows down the process of carbohydrate digestion and avoids postprandial hyperglycemia, which is a major cause of chronic diabetes-associated complication. This study was designed to evaluate the binding capacity of isolated alkaloids with targeted receptor. For this purpose, the three-dimensional tertiary structure of the α-glucosidase was generated by using the Molecular Operating Environment (MOE). The generated model was then validated by using the RAMPAGE and ERRAT server. The molecular docking of 37 alkaloids along with standard acarbose and miglitol reported as a α-glucosidase inhibitor was performed via MOE-Dock implemented in MOE software to find the binding modes of these inhibitors. The results showed that compound 17 (oriciacridone F) and 24 (O-methylmahanine) demonstrated marked interaction with active residues and were comparable to standard inhibitors. In short, this study provided computational background to the reported α-glucosidase inhibitors and thus further detail studies could lead to novel effective compounds.
Biology
Diabetes is a chronic disease with a high mortality rate worldwide and can cause other diseases such as kidney damage, narrowing of blood vessels, and heart disease. The concomitant use of drugs such as metformin, sulfonylurea, miglitol, and acarbose may cause side effects with long-term administration. Therefore, natural ingredients are the best choice, considering that their long-term side effects are not significant. One of the compounds that can be used as a candidate antidiabetic is mangostin; however, information on the molecular mechanism needs to be further analyzed through molecular docking, simulating molecular dynamics, and testing the in silico antidiabetic potential. This study focused on modeling the protein structure, molecular docking, and molecular dynamics simulations and analyses. This process produces RMSD values, free energies, and intermolecular hydrogen bonding. Based on the analysis results, all molecular dynamics simulations can occur under physiological con...
Journal of Pharmacy & Pharmacognosy Research, 2024
Context: The search for a safe and effective anti-diabetic medication has escalated due to the unfavorable side effects of synthetic drugs and the geometric rise in diabetes mellitus cases. Ruellia tuberosa is an important medicinal plant that can potentially reduce postprandial hyperglycemia. Aims: To identify the inhibition of aldose reductase, dipeptidyl peptidase 4 (DPP-4), and α-glucosidase for anti-diabetic drug discovery from Ruellia tuberosa bioactive compounds using computational methods, including molecular docking, binding free energy estimates and ADMET predictions. Methods: A molecular docking study of betulin, betulinic acid, cirsiliol, cirsimarin, cirsimaritin, and pedalitin with aldose reductase, DPP-4, and α-glucosidase inhibitors was done using Glide XP-docking module. The adsorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was carried out by the QikProp module, and ligand binding energy was ascertained by the prime molecular mechanics with generalized born and surface area (MM/GBSA) module, Schrodinger suite 2020-2. Results: The molecular docking and complexes' MM/GBSA show specific interactions and high binding free energies. The ADMET prediction demonstrates the excellent safety profile, pharmacokinetic characteristics, and favorable drug-likeness of betulin, betulinic acid, cirsiliol, cirsimarin, cirsimaritin, and pedalitin. This study shows the inhibition potential of Ruellia tuberosa compounds against aldose reductase, DPP-4, and α-glucosidase inhibitors. Conclusions: Therefore, for this chemical to be developed further into novel pharmaceuticals for treating type 2 diabetes mellitus, optimization and experimental research are required.