Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20

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• 作者：Elena Riva ; Daniela Comi ; Stella Borrelli ; Francesco Colombo ; Bruno Danieli ; Jurgen Borlak ; Lasse Evensen ; James B. Lorens ; Gabriele Fontana ; Ornella Maria Gia ; Lisa Dalla Via ; Daniele Passarella
• 关键词：Camptothecin derivative ; Topoisomerase inhibition ; Inhibition of angiogenesis
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：15 December 2010
• 年：2010
• 卷：18
• 期：24
• 页码：8660-8668
• 全文大小：819 K

文摘

The preparation and biological evaluation of a novel series of dimeric camptothecin derivatives are described. All the new compounds showed a significant ability to inhibit human tumor cell growth with IC₅₀ values ranging from 0.03 to 12.2 μM. The interference with the activity of the nuclear enzymes topoisomerases has been demonstrated, highlighting the poison effect of one of the obtained byproducts toward topoisomerase I. A moderate antiangiogenic activity has been demonstrated for one of the obtained compounds. Moreover, the effects of four new compounds on caspases activity and ROS generation have been studied on transgenic mouse cell.