Scientific article
English

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

Published inEuropean journal of pharmaceutical sciences, vol. 38, no. 1, p. 39-46
Publication date2009
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/genetics
  • Biological Transport/drug effects
  • Cell Line
  • Flavonoids/chemistry/pharmacology
  • Humans
  • Hydrogen Bonding
  • Hydrophobicity
  • Least-Squares Analysis
  • Mitoxantrone/metabolism
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Morus/chemistry
  • Neoplasm Proteins/antagonists & inhibitors/chemistry/genetics
  • Plant Bark/chemistry
  • Principal Component Analysis
  • Quantitative Structure-Activity Relationship
  • Reproducibility of Results
  • Surface Properties
  • Transfection
Citation (ISO format)
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. doi: 10.1016/j.ejps.2009.05.012
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Article (Published version)
accessLevelRestricted
Identifiers
Journal ISSN0928-0987
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