Synthesis, biological activity and receptor-based 3-D QSAR study of 3'-N-substituted-3'-N-debenzoylpaclitaxel analogues.
3'-N-Substituted-3'-N-debenzoylpaclitaxel analogues were synthesized and investigated for their 3-D QSAR by using comparative molecular field analysis (CoMFA). The CoMFA model obtained from receptor(microtubule)-paclitaxel binding structure displays an excellent predictive power to forecast the biological activity of new 3'-N-substituted-3'-N-debenzoylpaclitaxel analogues as well as the ability to explain the activity of the known paclitaxel analogues. The cross-validated r(2)(cv) values of the selected models are 0.835 and 0.616 for A549 and SK-OV-3, respectively, and the non-cross-validated r(2)(ncv) values of them are 0.992 and 0.974.
Roh
Eun Joo
EJ
Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, Republic of Korea.
Kim
Deukjoon
D
Choi
Jun Yong
JY
Lee
Bon Su
BS
Lee
Chong Ock
CO
Song
Choong Eui
CE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017239:Paclitaxel