Synthesis and biological evaluation of bis and monocarbonate prodrugs of 10-hydroxycamptothecins

Bioorganic & Medicinal Chemistry
Xungui HeJian Ding

Abstract

In an effort to improve the stability of labile lactone ring of camptothecins, the bis and mono-alkyl carbonate prodrugs of 10-hydroxycamptothecins were synthesized and their chemical and enzymatical stability as well as antitumor activity were studied. The in vitro evaluation of the stability of these carbonates indicates that the 10,20-biscarbonates are firstly hydrolyzed to afford the stable 20-monocarbonates. And the 10-carbonates are not stable in human plasma, mouse plasma and pH7.4 phosphate buffer, while the 20-carbonates are relatively stable in the three media and can be readily cleaved by porcine liver esterase. The overall toxicity of the tested carbonate against mice bearing S180 sarcoma is much lower when compared with the parent compound, and the antitumor activity is maintained.

Citations

Oct 23, 2008·Journal of Medicinal Chemistry·Sung-Ju MoonDavid M Goldenberg
Apr 1, 2011·Natural Product Research·Ying-Qian LiuHong-Yu Li
Jun 10, 2009·International Journal of Pharmaceutics·Xiaohui PuZhonggui He
Mar 4, 2008·European Journal of Medicinal Chemistry·Ying-Qian LiuZong-Cheng Zhan
Mar 29, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Linxia XiaoQingyong Li
Mar 19, 2021·Chemical Society Reviews·Yufei XueNicolas Hans Voelcker
Jul 27, 2010·Bioorganic & Medicinal Chemistry Letters·Bong-Seop LeeJohn S Yu

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