Alternative QSAR models for selected estradiol and cytochrome P450 ligands: comparison between classical, spectroscopic, CoMFA and GRID/GOLPE methods.
The performance of the spectroscopic EVA (eigenvalue) and EEVA (electronic eigenvalue) methods was tested with data sets applying coumarin 7-hydroxylation inhibitors (28 compounds) for cytochrome P450 mouse CYP2A5 and human CYP2A6 enzymes and 11ss-, 16a-, and 17a-substituted estradiol derivatives (30 compounds) for the lamb uterine estrogen receptor, and compared with the performance of the classical Hansch-type, CoMFA and GRID/GOLPE methods. Besides the internal predictability, the external predictability of the models was tested with several randomized training and test sets to ensure the validity and reliability of the models. Partial least squares (PLS) regression was employed as a general statistical tool with the EVA and EEVA methods. Some supplementary models were also built using only one PLS component with McGowan's volumes (MgVol and MgVol(2)) as additional descriptors and employing multiple linear regression (MLR) as the modelling tool. In general, both the internal and external performance of the EVA model, and more especially the EEVA model, with one PLS component and MgVol parameters was satisfactory, being either as good as or clearly better than that of the Hansch-type, CoMFA and GRID/GOLPE models.
Asikainen
A H
AH
Department of Environmental Sciences, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. Arja.Asikainen@uku.fi
Ruuskanen
J
J
Tuppurainen
K A
KA
D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D004958:Estradiol / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013057:Spectrum Analysis / Q000379:methods*
D008024:Ligands; D009281:Naphthalenes; C031721:naphthalene; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System