[Synthesis and antitumor activity of 20-O-linked camptothecin ester derivatives].
OBJECTIVE
To improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed.


METHODS
These derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H22 in mice.


RESULTS
Twelve derivatives of camptothecin ester are new compounds.


CONCLUSIONS
In vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H22 mouse liver tumoral model.
Pan
Xian-dao
XD
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. xdp@imm.ac.cn
Liu
Hong-yan
HY
Sun
Piao-yang
PY
Zhu
Cheng-gen
CG
Yang
Jing
J
Yuan
Kai-hong
KH
Han
Rui
R
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004952:Esters / Q000737:chemistry; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D019772:Topotecan / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004952:Esters; C496393:topotecan-20-O-(4-fluorophenoxyacetate); D019772:Topotecan; D002166:Camptothecin