Cargando…

Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study

Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most success...

Descripción completa

Detalles Bibliográficos
Autores principales: Kalhotra, Poonam, Chittepu, Veera C. S. R., Osorio-Revilla, Guillermo, Gallardo-Velázquez, Tzayhri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100528/
https://www.ncbi.nlm.nih.gov/pubmed/29882783
http://dx.doi.org/10.3390/molecules23061368
_version_ 1783348895375425536
author Kalhotra, Poonam
Chittepu, Veera C. S. R.
Osorio-Revilla, Guillermo
Gallardo-Velázquez, Tzayhri
author_facet Kalhotra, Poonam
Chittepu, Veera C. S. R.
Osorio-Revilla, Guillermo
Gallardo-Velázquez, Tzayhri
author_sort Kalhotra, Poonam
collection PubMed
description Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most successful source of potential leads or hits in the process of drug discovery and drug development. Recently, novel serine protease dipeptidyl peptidase-4 (DPP-4) inhibitors played a role in the management of diabetes, obesity, and cancer. This study describes the development of field template, field-based qualitative structure–activity relationship (SAR) model demonstrating DPP-4 inhibitors of natural origin, and the same model is used to screen virtually focused food database composed of polyphenols as potential DPP-4 inhibitors. Compounds’ similarity to field template, and novelty score “high and very high”, were used as primary criteria to identify novel DPP-4 inhibitors. Molecular docking simulations were performed on the resulting natural compounds using FlexX algorithm. Finally, one natural compound, chrysin, was chosen to be evaluated experimentally to demonstrate the applicability of constructed SAR model. This study provides the molecular insights necessary in the discovery of new leads as DPP-4 inhibitors, to improve the potency of existing DPP-4 natural inhibitors.
format Online
Article
Text
id pubmed-6100528
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61005282018-11-13 Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study Kalhotra, Poonam Chittepu, Veera C. S. R. Osorio-Revilla, Guillermo Gallardo-Velázquez, Tzayhri Molecules Article Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most successful source of potential leads or hits in the process of drug discovery and drug development. Recently, novel serine protease dipeptidyl peptidase-4 (DPP-4) inhibitors played a role in the management of diabetes, obesity, and cancer. This study describes the development of field template, field-based qualitative structure–activity relationship (SAR) model demonstrating DPP-4 inhibitors of natural origin, and the same model is used to screen virtually focused food database composed of polyphenols as potential DPP-4 inhibitors. Compounds’ similarity to field template, and novelty score “high and very high”, were used as primary criteria to identify novel DPP-4 inhibitors. Molecular docking simulations were performed on the resulting natural compounds using FlexX algorithm. Finally, one natural compound, chrysin, was chosen to be evaluated experimentally to demonstrate the applicability of constructed SAR model. This study provides the molecular insights necessary in the discovery of new leads as DPP-4 inhibitors, to improve the potency of existing DPP-4 natural inhibitors. MDPI 2018-06-06 /pmc/articles/PMC6100528/ /pubmed/29882783 http://dx.doi.org/10.3390/molecules23061368 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kalhotra, Poonam
Chittepu, Veera C. S. R.
Osorio-Revilla, Guillermo
Gallardo-Velázquez, Tzayhri
Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study
title Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study
title_full Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study
title_fullStr Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study
title_full_unstemmed Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study
title_short Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study
title_sort structure–activity relationship and molecular docking of natural product library reveal chrysin as a novel dipeptidyl peptidase-4 (dpp-4) inhibitor: an integrated in silico and in vitro study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100528/
https://www.ncbi.nlm.nih.gov/pubmed/29882783
http://dx.doi.org/10.3390/molecules23061368
work_keys_str_mv AT kalhotrapoonam structureactivityrelationshipandmoleculardockingofnaturalproductlibraryrevealchrysinasanoveldipeptidylpeptidase4dpp4inhibitoranintegratedinsilicoandinvitrostudy
AT chittepuveeracsr structureactivityrelationshipandmoleculardockingofnaturalproductlibraryrevealchrysinasanoveldipeptidylpeptidase4dpp4inhibitoranintegratedinsilicoandinvitrostudy
AT osoriorevillaguillermo structureactivityrelationshipandmoleculardockingofnaturalproductlibraryrevealchrysinasanoveldipeptidylpeptidase4dpp4inhibitoranintegratedinsilicoandinvitrostudy
AT gallardovelazqueztzayhri structureactivityrelationshipandmoleculardockingofnaturalproductlibraryrevealchrysinasanoveldipeptidylpeptidase4dpp4inhibitoranintegratedinsilicoandinvitrostudy