title: Phosphate ester derivatives of homocamptothecin: synthesis, solution stabilities and antitumor activities.
abstract: Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: You
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Jiangzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Liu
authors.forename: Linjian
authors.initials: L
authors.lastname: Zhu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cheng
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Che
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Chuan
authors.initials: C
authors.lastname: Luo
authors.forename: Yulan
authors.initials: Y
authors.lastname: Xu
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019999:Pharmaceutical Solutions; D010710:Phosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D019999:Pharmaceutical Solutions; D010710:Phosphates; C120029:homocamptothecin; D002166:Camptothecin