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

Poonam Kalhotra, Veera C.S.R. Chittepu, Guillermo Osorio-Revilla, Tzayhri Gallardo-Velázquez

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1368
JournalMolecules
Volume23
Issue number6
DOIs
StatePublished - 1 Jan 2018

Fingerprint

Dipeptidyl-Peptidase IV Inhibitors
Biological Products
Computer Simulation
inhibitors
products
obesity
diets
Nutrition
Medical problems
Dipeptidyl Peptidase 4
drugs
templates
Molecular Docking Simulation
Obesity
cancer
Diet
Vegetables
Polyphenols
Serine Proteases
protease

Keywords

  • Dipeptidyl peptidase-4 enzyme
  • Field-based virtual screening
  • Molecular docking
  • Natural products
  • Structure–activity relationship model

Cite this

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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",
abstract = "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.",
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