TY - JOUR
T1 - Structure–activity relationship and molecular docking of natural product library reveal chrysin as a novel dipeptidyl peptidase-4 (DPP-4) inhibitor
T2 - An integrated in silico and in vitro study
AU - Kalhotra, Poonam
AU - Chittepu, Veera C.S.R.
AU - Osorio-Revilla, Guillermo
AU - Gallardo-Velázquez, Tzayhri
N1 - Publisher Copyright:
© 2018 by the authors.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Dipeptidyl peptidase-4 enzyme
KW - Field-based virtual screening
KW - Molecular docking
KW - Natural products
KW - Structure–activity relationship model
UR - http://www.scopus.com/inward/record.url?scp=85048330374&partnerID=8YFLogxK
U2 - 10.3390/molecules23061368
DO - 10.3390/molecules23061368
M3 - Artículo
C2 - 29882783
AN - SCOPUS:85048330374
SN - 1420-3049
VL - 23
JO - Molecules
JF - Molecules
IS - 6
M1 - 1368
ER -