Phosphate ester derivatives of homocamptothecin: synthesis, solution stabilities and antitumor activities.
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.
Miao
Zhenyuan
Z
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
Zhang
Jing
J
You
Liang
L
Wang
Juan
J
Sheng
Chunquan
C
Yao
Jiangzhong
J
Zhang
Wannian
W
Feng
Hao
H
Guo
Wei
W
Zhou
Lei
L
Liu
Wenfeng
W
Zhu
Linjian
L
Cheng
Pengfei
P
Che
Xiaoying
X
Wang
Wenya
W
Luo
Chuan
C
Xu
Yulan
Y
Dong
Guoqiang
G
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
D000970:Antineoplastic Agents; D004952:Esters; D019999:Pharmaceutical Solutions; D010710:Phosphates; C120029:homocamptothecin; D002166:Camptothecin