Financial support from the Stehlin Foundation for Cancer Research.
Synthesis and anti-tumor activity of alkenyl camptothecin esters1
Version of Record online: 27 JAN 2005
Acta Pharmacologica Sinica
Volume 26, Issue 2, pages 235–241, February 2005
How to Cite
CAO, Z.-s., MENDOZA, J., DEJESUS, A. and GIOVANELLA, B. (2005), Synthesis and anti-tumor activity of alkenyl camptothecin esters. Acta Pharmacologica Sinica, 26: 235–241. doi: 10.1111/j.1745-7254.2005.00031.x
- Issue online: 27 JAN 2005
- Version of Record online: 27 JAN 2005
- Received 2004-07-02; Accepted 2004-10-27
- structure-activity relationship
Aim: 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.
Conclusion: 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.