Synthesis of novel α-santonin derivatives as potential cytotoxic agents

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• 作者：Francisco F.P. Arantes ; Luiz C.A. Barbosa ; Cé ; lia R.A. Maltha ; Antô ; nio J. Demuner ; Patricia Març ; al da Costa ; José ; R.O. Ferreira ; Letí ; cia V. Costa-Lotufo ; Manoel O. Moraes ; Clá ; udia Pessoa
• 关键词：Parishin A synthesis ; Sesquiterpene lactones ; α ; -methylene-γ ; -lactone ; Endoperoxide bridge ; Cytotoxicity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：45
• 期：12
• 页码：6045-6051
• 全文大小：215 K

文摘

Ten novel α-santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that α-methylene-γ-lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2–4, possessing the α-methylene-γ-lactone group showed IC₅₀ values between 5.70 and 16.40 ;c;M. Mixture of isomers 5 and 6, with the α-methylene-γ-lactone and endoperoxide functionalities, displayed the greatest activity, with IC₅₀ values between 1.45 and 4.35 ;c;M. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes.