3D-QSAR analysis of 2,4,5- and 2,3,4,5-substituted imidazoles as potent and nontoxic modulators of P-glycoprotein mediated MDR.
3D-Quantitative structure-activity relationships of 2,4,5- and 2,3,4,5-substituted imidazoles as a novel class of potent and nontoxic modulators of Pgp mediated MDR were investigated using CoMFA and COMSIA approaches. The best CoMFA model obtained from 46 imidazole analogues is a two-component model with the following statistics. R(2)(cv)=0.643, RMSE(cv)=0.360 for the cross-validation, and R(2)=0.767, RMSE=0.290 for the fitted. The best COMSIA model obtained is also a two-component model with the following statistics. R(2)(cv)=0.619, RMSE(cv)=0.372 for the cross-validation, and R(2)=0.765, RMSE=0.292 for the fitted.
Kim
K H
KH
Department of Structural Biology, Abbott Laboratories, Abbott Park, IL 60064-6100, USA. ki.h.kim@abbott.com
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism*; D003198:Computer Simulation; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008962:Models, Theoretical; D021281:Quantitative Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007093:Imidazoles; C410029:OC 144-093