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Title

Breast cancer resistance protein (BCRP/ABCG2): new inhibitors and QSAR studies by a 3D linear solvation energy approach

Authors
Guilet, David
Dijoux-Franca, Marie-Geneviève
Zelefac, Fabien
Macalou, Sira
Grosselin, Jeanne
Schmidt, Julien
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Published in European Journal of Pharmaceutical Sciences. 2009, vol. 38, no. 1, p. 39-46
Abstract A series of compounds derived from naturally occurring flavonoids and synthetic analogs have been evaluated on cell lines overexpressing the wild-type breast cancer resistance protein (BCRP/ABCG2) half-transporter. Human ABCG2-transfected cells were used for screening their inhibitory activity. Five new natural compounds obtained from Morus mesozygia Stapf and one synthetic chromone, comprising a flavonoidic scaffold, were also evaluated. Based on the results obtained with a total of 34 compounds, a 3D linear solvation energy QSAR was investigated by VolSurf descriptors of molecular-interaction fields (MIFs) related to hydrophobic-interaction forces, polarisability and hydrogen-bonding capacity. Accuracy of the constructed 3D-QSAR model was attested by a correlation coefficient r(2) of 0.77. Shape parameters and hydrophobicity were revealed to be major physicochemical parameters responsible for the inhibition activity of flavonoid derivatives and synthetic analogs towards ABCG2, whereas hydrogen-bond donor capacity appeared highly unfavorable.
Keywords ATP-Binding Cassette Transporters/antagonists & inhibitors/chemistry/geneticsBiological Transport/drug effectsCell LineFlavonoids/chemistry/pharmacologyHumansHydrogen BondingHydrophobicityLeast-Squares AnalysisMitoxantrone/metabolismModels, MolecularMolecular ConformationMolecular StructureMorus/chemistryNeoplasm Proteins/antagonists & inhibitors/chemistry/geneticsPlant Bark/chemistryPrincipal Component AnalysisQuantitative Structure-Activity RelationshipReproducibility of ResultsSurface PropertiesTransfection
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PMID: 19501160
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NICOLLE, Edwige et al. Breast cancer resistance protein (BCRP/ABCG2): new inhibitors and QSAR studies by a 3D linear solvation energy approach. In: European Journal of Pharmaceutical Sciences, 2009, vol. 38, n° 1, p. 39-46. https://archive-ouverte.unige.ch/unige:3979

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Deposited on : 2009-11-05

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