Synthesis and anti-tumor activity of alkenyl camptothecin esters.
OBJECTIVE
To study the degrees of influence of changing side ester chains at position C20 of camptothecin on the anti-tumor activity of the molecules.


METHODS
The esterification reaction of camptothecin 1 and 9-nitrocamptothecin 2 with crotonic anhydride in pyridine gave the corresponding esters 3 and 4, respectively. The acylation of 1 and 2 with cinnamoyl chloride gave products 7 and 8. Epoxidation reaction of 3 and 4 with m-chloroperoxybenzoic acid in benzene solvent gave the products 5 and 6. Esters 3, 4, and 5 were tested for anti-tumor activity against 14 human cancer cell lines.


RESULTS
Both in vitro and in vivo anti-tumor activity studies for these esters were conducted and the data demonstrated positive results, that is, these esters were active against the tested tumor lines.


CONCLUSIONS
Alkenyl esters 3 and 4 showed strong anti-tumor activity in vitro against 14 different cancer cell lines. Ester 3 was active against human breast carcinoma in mice and the toxicity of the agent was not observed in mice during the treatment, implying that this agent is effective for treatment with low toxicity.
Cao
Zhi-Song
ZS
Stehlin Foundation for Cancer Research and St Joseph Hospital Cancer Laboratory, 1918 Chenevert Street, Houston, Texas 77003, USA. zcao@stehlin.org
Mendoza
John
J
Dejesus
Albert
A
Giovanella
Beppino
B
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004952:Esters / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation
D000972:Antineoplastic Agents, Phytogenic; D004952:Esters; C079905:rubitecan; D002166:Camptothecin