Discovery of novel andrographolide derivatives as cytotoxic agents

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• 作者：Shanfu Wei ; Yan-Bo Tang ; Huiming Hua ; Emika Ohkoshi ; Masuo Goto ; Li-Ting Wang ; Kuo-Hsiung Lee ; Zhiyan Xiao
• 关键词：Andrographolide derivatives ; Labdane diterpenes ; Cytotoxicity ; Microtubule dynamics
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：15 July, 2013
• 年：2013
• 卷：23
• 期：14
• 页码：4056-4060
• 全文大小：2585 K

文摘

The natural diterpenoid andrographolide (1) exhibits various biological activities. Seventeen derivatives of 1 were prepared via esterification and etherification of 14-dehydroxy-11,12-didehydroandrographolide (2). Most derivatives demonstrated significant inhibition against tumor cell growth. The most active compounds, 3b and 3c, had GI₅₀ values of 1.46-9.19 ¦ÌM against A549, DU145, KB and KB-Vin tumor cells. In an immunocytochemical study, treatment with compound 3c disrupted microtubule dynamics in PC-3 cells, but caused no accumulation of metaphase cells, which is a phenotype dissimilar from that of 1. This difference suggests that structural modification of 1 resulted in a shift in the underlying molecular mechanism.