Synthesis of camptothecin derivatives

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Date

2005

Author

Duygu, Arife Neşe

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This study presents synthetic studies on camptothecin, a potent antitumor agent in order to improve its stability and solubility without reducing its activity. The study consists of the modification of camptothecin at 20-OH position a new strategy for the targeted and controlled release of the drug and modification at C-7 position to overcome the stability and solubility problems of the free drug. In the first part of the study, the 20-OH functional group of camptothecin was replaced with an unsymmetrical benzoin derivative that is able to release the drug under photolysis at 350 nm. The new prodrugs synthesized possessed higher stability than the camptothecin itself. The in vitro irradiation of the prodrugs at 350 nm was satisfactory without any decomposition of the active substance. The second part of the study comprises the studies on the modification of the 7th position of camptothecin, which is the most suitable position for the modification. In this part of the study, 7-amino and silyl substituted camptothecins were synthesized.Combination of camptothecin with some other drugs such as cisplatin was also investigated in this study. The synthetic efforts showed that the reactions are very promising and the combination studies can be studied as a major subject in the future.

Subject Keywords

Chemistry, Organic

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http://etd.lib.metu.edu.tr/upload/3/12606302/index.pdf
https://hdl.handle.net/11511/15297

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

A. N. Duygu, “Synthesis of camptothecin derivatives,” Ph.D. - Doctoral Program, Middle East Technical University, 2005.