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

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Nicolle E, Boccard J, Guilet D, Dijoux-Franca MG, Zelefac F, Macalou S, Grosselin J, Schmidt J, Carrupt PA, Di Pietro A, Boumendjel A

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

Eur J Pharm Sci. 2009 Aug 12;38(1):39-46. doi: 10.1016/j.ejps.2009.05.012. Epub 2009 Jun 6.

PubMed ID

19501160 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Mitoxantrone	ATP-binding cassette sub-family G member 2	Protein	Humans	Unknown	Substrate	Details