TY - JOUR
T1 - Breast cancer resistance protein (BCRP/ABCG2)
T2 - New inhibitors and QSAR studies by a 3D linear solvation energy approach
AU - Nicolle, Edwige
AU - Boccard, Julien
AU - Guilet, David
AU - Dijoux-Franca, Marie Geneviève
AU - Zelefac, Fabien
AU - Macalou, Sira
AU - Grosselin, Jeanne
AU - Schmidt, Julien
AU - Carrupt, Pierre Alain
AU - Di Pietro, Attilio
AU - Boumendjel, Ahcène
N1 - Funding Information:
This work was funded by the CNRS and the Université Lyon 1, and grants from the Agence Nationale de la Recherche (ANR-06-BLAN-0420), the Association pour la Recherche sur le Cancer (ARC 3942) and the Ligue Nationale contre le Cancer (Equipe Labellisée 2009). S.M. was recipient of a doctoral fellowship from the Ligue de la Loire and the ARC. The technical assistance of Sandrine Magnard is acknowledged. F.Z. is a recipient of an AUF grant to whom he is thankful.
PY - 2009/8/12
Y1 - 2009/8/12
N2 - 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 r2 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.
AB - 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 r2 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.
KW - 3D-QSAR
KW - BCRP
KW - Flavonoids
KW - VolSurf descriptors
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U2 - 10.1016/j.ejps.2009.05.012
DO - 10.1016/j.ejps.2009.05.012
M3 - Article
C2 - 19501160
AN - SCOPUS:67650220889
SN - 0928-0987
VL - 38
SP - 39
EP - 46
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
IS - 1
ER -