3D-QSAR studies on PU3 analogues by comparative molecular field analysis.
A comparative molecular field analysis (CoMFA) of PU3 derivatives of Hsp90 (Heat shock protein 90) inhibitors has been performed to determine the factors contributing the corresponding activities. The energy minimized conformations were obtained by molecular mechanics using SYBYL package. The developed model, with r(2) value of 0.947, was verified by performing leave-one out (LOO) cross-validation, which showed q(2) value of 0.513. The calculated model not only elucidates the relationship between compound structures and biological activities but, more importantly, facilitates design of new Hsp90 inhibitors with calculated antiproliferative activity.
Liu
Hong-Chong
HC
Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan 402, ROC.
Lyu
Ping-Chiang
PC
Leong
Max K
MK
Tsai
Keng-Chang
KC
Hsiue
Ging-Ho
GH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins