First synthesis of novel spin-labeled derivatives of camptothecin as potential antineoplastic agents.
In an effort to improve the stability of labile lactone ring and water solubility of camptothecin, five novel spin-labeled camptothecin derivatives were synthesized in quantitative yield by a simple modification of the carbodiimide method using the combination of scandium triflate (Sc(OTf)(3)) and 4-dimethylaminopyridine (DMAP), and the in vitro pharmacokinetic determination of the lactones of representative compound 13a showed that the biological life span of their lactone forms in human and mouse plasma significantly increased when compared with their mother compound camptothecin. Also, the in vitro cytotoxicity of compounds 13a-13e against human bladder cancer T-24 showed either similar or better activity than that of the parent drug, camptothecin, and clinically available drug, irinotecan.
Liu
Ying-Qian
YQ
School of Pharmacy, Lanzhou University, Lanzhou 730000, P R China. yqliu@lzu.edu.cn
Tian
Xuan
X
Yang
Liu
L
Zhan
Zong-Cheng
ZC
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D013113:Spin Labels / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D013113:Spin Labels; D002166:Camptothecin