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Food and Chemical Toxicology : An... Nov 2020Recently the use of bioactive α-glucosidase inhibitors for the treatment of diabetes have been proven to be the most efficient remedy for controlling postprandial... (Review)
Review
Recently the use of bioactive α-glucosidase inhibitors for the treatment of diabetes have been proven to be the most efficient remedy for controlling postprandial hyperglycemia and its detrimental physiological complications, especially in type 2 diabetes. The carbohydrate hydrolysing enzyme, α-glucosidase, is generally competitively inhibited by the α-glucosidase inhibitors and results in the delayed glucose absorption in small intestine, ultimately controlling the postprandial hyperglycemia. Here we have reviewed the most recent updates in the bioactive α-glucosidase inhibitors category. This review provides an overview of the α-glucosidase inhibitory potentials and efficiency of controlling postprandial hyperglycemia of various bioactive compounds such as flavonoids, phenolic compound, polysaccharide, betulinic acid, tannins, anthocyanins, steroids, polyol, polyphenols, galangin, procyanidins, hydroxyl-α-sanshool, hydroxyl-β-sanshool, erythritol, ganomycin, caffeoylquinic acid, resin glycosides, saponins, avicularin, oleanolic acids, urasolic acid, ethanolic extracts etc., from various dietary and non-dietary naturally occurring sources.
Topics: Animals; Diabetes Mellitus, Type 2; Glycoside Hydrolase Inhibitors; Humans; Molecular Structure; Plant Extracts; alpha-Glucosidases
PubMed: 32916220
DOI: 10.1016/j.fct.2020.111738 -
Current Opinion in Investigational... Oct 2004Genzyme General is developing recombinant human alpha-glucosidase, produced in mammalian cell culture, as a potential treatment for Pompe disease. By July 2004,... (Review)
Review
Genzyme General is developing recombinant human alpha-glucosidase, produced in mammalian cell culture, as a potential treatment for Pompe disease. By July 2004, enrollment was completed in two clinical trials and an observational study in adults. Genzyme was planning to file for regulatory approval in Europe during 2004, followed by filings in the US and Japan in mid-2005.
Topics: Animals; Clinical Trials as Topic; Glycogen Storage Disease Type II; Humans; Recombinant Proteins; Structure-Activity Relationship; Treatment Outcome; alpha-Glucosidases
PubMed: 15535432
DOI: No ID Found -
European Journal of Medicinal Chemistry Aug 2019α-Glucosidase enzyme inhibition is an effective therapeutic decorum in the treatment of type 2 diabetes mellitus. Since 1990, three α-glucosidase inhibitors are known... (Review)
Review
α-Glucosidase enzyme inhibition is an effective therapeutic decorum in the treatment of type 2 diabetes mellitus. Since 1990, three α-glucosidase inhibitors are known to exist clinically, Acarbose, Voglibose and Miglitol. Side effects and long synthetic routes to access them forced the researchers to move their focus to discover simple and small heterocyclic motifs that work as promising α-glucosidase inhibitors and may eventually lead to the management of postprandial hyperglycemic condition in T2DM. In this regards, this review deals with recently discovered heterocyclic molecules that have been evaluated to exhibit inhibition of α-glucosidase enzyme.
Topics: Animals; Cell Line, Tumor; Glycoside Hydrolase Inhibitors; Heterocyclic Compounds; Humans; Hypoglycemic Agents; Molecular Docking Simulation; Molecular Structure; Protein Binding; Structure-Activity Relationship; alpha-Glucosidases
PubMed: 31112894
DOI: 10.1016/j.ejmech.2019.04.025 -
Bioorganic & Medicinal Chemistry Letters Dec 2020In light of the adequate sources for Hylotelephium erythrostictum, its active components have aroused research interest....
In light of the adequate sources for Hylotelephium erythrostictum, its active components have aroused research interest. 2-(3',4'-dihydroxyphenyl)-2,3-dihydro-4,6-dihydroxy-2-(methoxy)- 3-benzofuranone(1), apigenin(2), diosmetin(3), kaempferol(4), kaempferide(5), rhamnocitrin(6), quercetin(7), and gallic acid(8) were isolated from H. erythrostictum. Rarely occurring naturally, 1 is 2-methoxybenzofuranone type compound against α-glucosidase and exhibits a potential inhibitory effect on α-glucosidase(IC = 1.8 μM), with a Ki value of 709 nM. In silico molecular docking was performed for the investigation of the inhibition mechanism. H. erythrostictum is a potential source of antidiabetic agent. This information is useful in finding more potent antidiabetic candidates from medicinal plants for the clinical development of therapeutics.
Topics: Catalytic Domain; Crassulaceae; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Molecular Docking Simulation; Plant Extracts; alpha-Glucosidases
PubMed: 33152378
DOI: 10.1016/j.bmcl.2020.127665 -
Mini Reviews in Medicinal Chemistry 2015A natural pentacyclic triterpenoid oleanolic acid 1 and its biotransformed metabolites 2-3 are potential α-glucosidase inhibitors. To elucidate the inhibitory mechanism... (Review)
Review
A natural pentacyclic triterpenoid oleanolic acid 1 and its biotransformed metabolites 2-3 are potential α-glucosidase inhibitors. To elucidate the inhibitory mechanism of compounds 1, 2 and 3 against α-glucosidase, we calculated (i) their electronic and optical properties using DFT and TD-DFT at the B3LYP/6-31G(d) level in gas and IEF-PCM solvent; and (ii) their binding energies to α-glucosidase via docking study. DFT results showed that the α-glucosidase inhibtion is mainly depend on the polarity parameters of the studied compounds. Docking results revealed that the activity increased with binding energies (i.e. the stability of ligand-receptor complex). The specroscopic data of oleanolic acid 1 and its metabolites 2 and 3 are well predicetd for 13C NMR chemical shifts (R2=99%) and 1H NMR chemical shifts (R2=90%); and for (ii) UV/vis spectra. The assignments and interpretation of NMR chemical shifts and bathochromic shift of λMAX absorption bands are discussed.
Topics: Enzyme Activation; Glycoside Hydrolase Inhibitors; Humans; Molecular Conformation; Molecular Docking Simulation; Oleanolic Acid; Oxidation-Reduction; Quantum Theory; alpha-Glucosidases
PubMed: 26205959
DOI: 10.2174/1389557515666150724154044 -
Molecules (Basel, Switzerland) Jul 2023To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (-) were screened for their α-glucosidase inhibitory effects. All derivatives...
To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (-) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC value: 640.57 ± 5.13 μM). In particular, compound displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds , , , , and were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds , , , , and and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound were also investigated.
Topics: Molecular Structure; Structure-Activity Relationship; Acarbose; Molecular Docking Simulation; alpha-Glucosidases; Kinetics; Glycoside Hydrolase Inhibitors; Isoquinolines
PubMed: 37446942
DOI: 10.3390/molecules28135282 -
Natural Product Research May 2021To find a potent -glucosidase inhibitor, 24 tyrosol derivatives with different substituents located at the , , or position of the phenyl group have been synthesised via...
To find a potent -glucosidase inhibitor, 24 tyrosol derivatives with different substituents located at the , , or position of the phenyl group have been synthesised via the Mitsunobu reaction, characterised by H NMR, C NMR, ESI-MS and IR and evaluated for inhibition. The derivatives possessed varying degrees of inhibitory activity against -glucosidase and a relationship between the structure and activity was subsequently established for all compounds. Two of these compounds with substituents at the position showed significant inhibitory effects surpassing that of the control standard acarbose. Molecular docking studies performed to better understand the binding interactions between the enzyme and the two most active compounds showed substantial binding within the active site of -glucosidase. Taken together, these results indicate that the position of the substituent plays a crucial role in this inhibition and may facilitate the development of new -glucosidase inhibitors.
Topics: Acarbose; Binding Sites; Catalytic Domain; Glycoside Hydrolase Inhibitors; Molecular Docking Simulation; Phenylethyl Alcohol; Structure-Activity Relationship; Yeasts; alpha-Glucosidases
PubMed: 31204495
DOI: 10.1080/14786419.2019.1628750 -
Fitoterapia Dec 2023Rice husk is one of the most plentiful agriculture by-products in rice producing areas, which harbors a substantial proportion of biological metabolites, however, it has...
Rice husk is one of the most plentiful agriculture by-products in rice producing areas, which harbors a substantial proportion of biological metabolites, however, it has not been well studied. As an attempt to utilize it as a productive manner, phytochemical investigation on rice husk has performed and led to the isolation of three undescribed (1, 2, and 7), along with twelve known components (3-6, and 8-15). Those chemical structures were elucidated based on massive spectroscopic methods. Among them, compounds 4, 6-8, and 10-13 have been shown to act as α-glucosidase inhibitors. Notably, the most active compounds, 10/11, demonstrated comparable α-glucosidase inhibitory effect (IC = 1.83 ± 0.11 μg/mL) to that of 1-deoxynojirimycin (IC = 1.02 ± 0.16 μg/mL). For the molecular docking simulation studies, compounds 10/11 showed relative binding interactions with α-glucosidase enzyme (PDB ID: 3A4A) that similar to those reference inhibitors. Additionally, the crude extract of O. sativa demonstrated better α-glucosidase inhibitory effect to that of isolated components, with the IC value at 1.25 ± 0.07 μg/mL.
Topics: Glycoside Hydrolase Inhibitors; Oryza; Molecular Structure; alpha-Glucosidases; Molecular Docking Simulation; Plant Extracts
PubMed: 37757924
DOI: 10.1016/j.fitote.2023.105688 -
Daru : Journal of Faculty of Pharmacy,... Jun 2020One of the therapeutic approaches in the management of Type 2 diabetes is delaying the absorption of glucose through α-glucosidase enzymes inhibition, which can reduce...
PURPOSE
One of the therapeutic approaches in the management of Type 2 diabetes is delaying the absorption of glucose through α-glucosidase enzymes inhibition, which can reduce the incidence of postprandial hyperglycemia. The existence of chronic postprandial hyperglycemia impaired the endogenous antioxidant defense due to inducing oxidative stress induced pancreatic β-cell destruction through uncontrolled free radicals generation such as ROS, which in turn, leads to various macrovascular and microvascular complications. This study aimed to synthesize 2-aryl-4,6-diarylpyrimidine derivatives, screen their α-glucosidase inhibitory activity, perform kinetic and molecular docking studies.
METHODS
A series of 3,4,5-triphenyl-4,5-dihydro-1,2,4-oxadiazole derivatives were synthesized and their α-glucosidase inhibitory activity was screened in vitro. Compounds 6a-k were synthesized via a two-step reaction with a yield between 65 and 88%. The structural elucidation of the synthesized derivatives was performed by different spectroscopic techniques. α-Glucosidase inhibitory activity of the oxadiazole derivatives 6a-k was evaluated against Saccharomyces cerevisiae α-glucosidase.
RESULTS
Most of the synthesized compounds demonstrated α-glucosidase inhibitory action. Particularly compounds 6c, 6d and 6 k were the most active compounds with IC values 215 ± 3, 256 ± 3, and 295 ± 4 μM respectively. A kinetic study performed for compound 6c revealed that the compound is a competitive inhibitor of Saccharomyces cerevisiae α-glucosidase with K of 122 μM. The docking study also revealed that the two compounds, 6c and 6 k, have important binding interactions with the enzyme active site.
CONCLUSION
The overall results of our study reveal that the synthesized compounds could be a potential candidate in the search for novel α-glucosidase inhibitors to manage the postprandial hyperglycemia incidence. Graphical abstract.
Topics: Glycoside Hydrolase Inhibitors; Kinetics; Molecular Docking Simulation; Oxadiazoles; Saccharomyces cerevisiae; alpha-Glucosidases
PubMed: 31907787
DOI: 10.1007/s40199-019-00322-y -
Mini Reviews in Medicinal Chemistry 2020α-Glucosidase plays an important role in carbohydrate metabolism and is an attractive drug target for the treatment of diabetes, obesity and other related... (Review)
Review
α-Glucosidase plays an important role in carbohydrate metabolism and is an attractive drug target for the treatment of diabetes, obesity and other related complications. Currently, acarbose, miglitol and voglibose have been approved by the FDA for the treatment of diabetes by oral α-glucosidase inhibitors. With the development of anti-diabetic drugs, the emergence of novel drugs with various chemotypes has overshadowed α-glucosidase inhibitors. Since the 1990s, the FDA has not approved new chemical entities against α-glucosidase, which has resulted in restricted clinical medication. Nevertheless, this type of inhibitors possess several unparalleled advantages over other drugs, especially mild side effects (non-systemic gastrointestinal side effects and occasional allergic reactions). Additionally, α-glucosidase inhibitors for monotherapy or in combination with other drugs have been proved to be a feasible approach for the treatment of diabetes. In the last decade, the discovery of natural or synthetic indole derivatives possessing the inhibitory activity of α-glucosidase has received great attention. Herein, we have summarized indoles as inhibitors of α-glucosidase activity, their mechanism of action, synthetic methodologies and structure-activity relationships. Moreover, we have compared the inhibitory potencies of all compounds under their corresponding positive control as well as oral absorption in silico evaluated by tPSA. This review will provide a medium on which future drug design and development for the treatment of diabetes may be modeled as many drug candidates with present great potential as effective anti-diabetic chemotherapy.
Topics: Glycoside Hydrolase Inhibitors; Humans; Indoles; Molecular Structure; Structure-Activity Relationship; alpha-Glucosidases
PubMed: 32560604
DOI: 10.2174/1389557520666200619121003