α-Glucosidase inhibition by flavonoids: an  in vitro  and  in silico  structure–activity relationship study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme’s activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure–activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC ₅₀ much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.

Abstract

Related collections

Most cited references 49

Record: found
Abstract: found
Article: not found

Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes.

M. D. Eldridge, C. Murray, T Auton … (1997)

This paper describes the development of a simple empirical scoring function designed to estimate the free energy of binding for a protein-ligand complex when the 3D structure of the complex is known or can be approximated. The function uses simple contact terms to estimate lipophilic and metal-ligand binding contributions, a simple explicit form for hydrogen bonds and a term which penalises flexibility. The coefficients of each term are obtained using a regression based on 82 ligand-receptor complexes for which the binding affinity is known. The function reproduces the binding affinity of the complexes with a cross-validated error of 8.68 kJ/mol. Tests on internal consistency indicate that the coefficients obtained are stable to changes in the composition of the training set. The function is also tested on two test sets containing a further 20 and 10 complexes, respectively. The deficiencies of this type of function are discussed and it is compared to approaches by other workers.

0 comments Cited 191 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Role of Reactive Oxygen Species in the Progression of Type 2 Diabetes and Atherosclerosis

Hideaki Kaneto, Naoto Katakami, Munehide Matsuhisa … (2010)

Type 2 diabetes is the most prevalent and serious metabolic disease all over the world, and its hallmarks are pancreatic β-cell dysfunction and insulin resistance. Under diabetic conditions, chronic hyperglycemia and subsequent augmentation of reactive oxygen species (ROS) deteriorate β-cell function and increase insulin resistance which leads to the aggravation of type 2 diabetes. In addition, chronic hyperglycemia and ROS are also involved in the development of atherosclerosis which is often observed under diabetic conditions. Taken together, it is likely that ROS play an important role in the development of type 2 diabetes and atherosclerosis.

0 comments Cited 138 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Comparative evaluation of quercetin, isoquercetin and rutin as inhibitors of alpha-glucosidase.

J. Bian, F Shan, F Zhou … (2009)

Three flavonoids from tartary buckwheat bran, namely, quercetin (Que), isoquercetin (Iso) and rutin (Rut), have been evaluated as alpha-glucosidase inhibitors by fluorescence spectroscopy and enzymatic kinetics and have also been compared with the market diabetes healer, acarbose. The results indicated that Que, Iso and Rut could bind alpha-glucosidase to form a new complex, which exhibited a strong static fluorescence quenching via nonradiation energy transfer, and an obvious blue shift of maximum fluorescence. The sequence of binding constants (K(A)) was Que > Iso > Rut, and the number of binding sites was one for all of the three cases. The thermodynamic parameters were obtained by calculations based on data of binding constants. They revealed that the main driving force of the above-mentioned interaction was hydrophobic. Enzymatic kinetics measurements showed that all of the three compounds were effective inhibitors against alpha-glucosidase. Inhibitory modes all belonged to a mixed type of noncompetitive and anticompetitive. The sequence of affinity (1/K(i)) was in accordance with the results of binding constants (K(A)). The concentrations which gave 50% inhibition (IC(50)) were 0.017 mmol*L(-1), 0.185 mmol*L(-1) and 0.196 mmol*L(-1), compared with acarbose's IC(50) (0.091 mmol*L(-1)); the dose of acarbose was almost five times of that of Que and half of that of Iso and Rut. Our results explained why the inhibition on alpha-glucosidase of tartary buckwheat bran extractive substance (mainly Rut) was much weaker than that of its hydrolysis product (a mixture of Que, Iso and Rut). This work would be significant for the development of more powerful antidiabetes drugs and efficacious utilization of tartary buckwheat, which has been proved as an acknowledged food in the diet of diabetic patients.

0 comments Cited 98 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Enzyme Inhib Med Chem

Journal ID (iso-abbrev): J Enzyme Inhib Med Chem

Journal ID (publisher-id): IENZ

Journal ID (publisher-id): ienz20

Title: Journal of Enzyme Inhibition and Medicinal Chemistry

Publisher: Taylor & Francis

ISSN (Print): 1475-6366

ISSN (Electronic): 1475-6374

Publication date Collection: 2017

Publication date (Electronic): 21 September 2017

Volume: 32

Issue: 1

Pages: 1216-1228

Affiliations

[a ] UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Porto, Portugal;

[b ] UCIBIO, REQUIMTE, Faculty of Sciences, Department of Chemistry and Biochemistry, University of Porto , Porto, Portugal;

[c ] Department of Chemistry & QOPNA, University of Aveiro , Aveiro, Portugal

Author notes

Supplemental data for this article can be accessed here .

CONTACT Eduarda Fernandes egracas@ 123456ff.up.pt UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Porto, Portugal;

Pedro A. Fernandes pafernan@ 123456fc.up.pt UCIBIO, REQUIMTE, Faculty of Sciences, Department of Chemistry and Biochemistry, University of Porto , Porto, Portugal

Author information

Eduarda Fernandes http://orcid.org/0000-0001-6424-0976

Article

Publisher ID: 1368503

DOI: 10.1080/14756366.2017.1368503

PMC ID: 6009965

PubMed ID: 28933564

SO-VID: 01d89db0-1687-482d-8a05-63e4154d4501

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 31 May 2017

Date revision received : 27 July 2017

Date accepted : 04 August 2017

Page count

Pages: 13, Words: 9082

Funding

Funded by: Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência 10.13039/501100001871

Funded by: European Union funds

Award ID: PT2020 UID/MULTI/04378/2013 – POCI/01/0145/FEDER/007728

Award ID: FCT UID/QUI/00062/2013

Award ID: NORTE-01–0145-FEDER-000024

Funded by: Programa Operacional Competitividade e Internacionalização

Award ID: PTDC/QEQ-QAN/1742/2014 – POCI-01–0145-FEDER-016530

Funded by: FCT 10.13039/100006136

Award ID: SFRH/BD/116005/2016

Funded by: Fundo Social Europeu

Funded by: Ministério da Ciência, Tecnologia e Ensino Superior 10.13039/501100006111

The authors acknowledge the financial support from National funds [Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência (FCT/MEC)] and European Union funds [Fundo Europeu de Desenvolvimento Regional (FEDER)] under the program PT2020 (PT2020 UID/MULTI/04378/2013 - POCI/01/0145/FEDER/007728), the framework of QREN (NORTE-01-0145-FEDER-000024), and Programa Operacional Competitividade e Internacionalização (COMPETE). Carina Proença acknowledges FCT the financial support for the PhD grant (SFRH/BD/116005/2016), in the ambit of “QREN - POPH - Tipologia 4.1 - Formação Avançada”, co-sponsored by Fundo Social Europeu (FSE) and by national funds of Ministério da Ciência, Tecnologia e Ensino Superior (MCTES). Daniela Ribeiro acknowledges FEDER, through COMPETE and FCT, the financial support for the Post-doc grant in the ambit of the project PTDC/QEQ-QAN/1742/2014 - POCI-01-0145-FEDER-016530.

α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study

Read this article at

Abstract

Abstract

Related collections

Drug_transporters

Most cited references 49

Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes.

Role of Reactive Oxygen Species in the Progression of Type 2 Diabetes and Atherosclerosis

Comparative evaluation of quercetin, isoquercetin and rutin as inhibitors of alpha-glucosidase.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 571

Cited by 81

Most referenced authors 1,977