Synthesis and cytotoxic activity of new 9-substituted camptothecins
- 作者：Sabrina Dallavalle ; Daniela Granza Rocchetta ; Loana Musso ; Lucio Merlini ; Gabriella Morini ; Sergio Penco ; Stella Tinelli ; Giovanni Luca Beretta ; Franco Zunino
- 关键词：Camptothecin ; Antitumor agents ; Topoisomerase I ; DNA cleavage ; Synthesis
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 May 2008
- 卷：18
- 期：9
- 页码：2781-2787
- 文件大小：507 K
摘要
A series of novel 9-substituted camptothecins derived from 9-formylcamptothecin were synthesized. The aldehyde was obtained from 10-hydroxycamptothecin or, better, by total synthesis. The compounds showed antiproliferative activity higher than that of the reference compound topotecan. Modelling suggested the possibility of a favourable interaction of small and polar 9-substituents with the topoisomerase I–DNA complex, which is consistent with the higher activity of these derivatives with respect to the corresponding 7-substituted camptothecins.