Synthesis and Structure-Activity Relationships of New Benzodioxinic Lactones as Potential Anticancer Drugs

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• 作者：Manel Romero ; Pierre Renard ; Daniel-Henry Caignard ; Ghanen Atassi ; Xavier Solans ; Pere Constans ; Christian Bailly ; Maria Dolors Pujol
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：January 25, 2007
• 年：2007
• 卷：50
• 期：2
• 页码：294 - 307
• 全文大小：387K
• 年卷期：v.50,no.2(January 25, 2007)
• ISSN：1520-4804

文摘

A set of disubstituted tetracyclic lactones has been synthesized and tested for potential antitumor activity.Several of them possess a noticeable cytotoxicity against L1210 and HT-29 colon cells in vitro. Relationshipsbetween chain nature and biological properties were sought. Lactones with a pentyl or hexyl substituent atC-11 are the most active ones. The introduction of a functional group at the side chain of C-11 modified thepotency; carboxylic acid and primary amine decreased the cytotoxicity, whereas a cyano group increasedthe activity. An extensive structure-activity relationship study of these derivatives, including carbonhomologues and bioisosteres has been performed. The synthesis and cytotoxicity of these compounds arediscussed. Two lactones are recognized as potential lead compounds.