title: First synthesis of novel spin-labeled derivatives of camptothecin as potential antineoplastic agents.
abstract: 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.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, P R China. yqliu@lzu.edu.cn
authors.forename: Ying-Qian
authors.initials: YQ
authors.lastname: Liu
authors.forename: Xuan
authors.initials: X
authors.lastname: Tian
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Zong-Cheng
authors.initials: ZC
authors.lastname: Zhan
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D013113:Spin Labels; D002166:Camptothecin