1. Discovery of novel andrographolide derivatives as cytotoxic agents.
- Author
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Wei, Shanfu, Tang, Yan-Bo, Hua, Huiming, Ohkoshi, Emika, Goto, Masuo, Wang, Li-Ting, Lee, Kuo-Hsiung, and Xiao, Zhiyan
- Subjects
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DITERPENES , *ORGANIC compound derivatives , *ANTINEOPLASTIC agents , *ESTERIFICATION , *ETHERIFICATION , *CANCER cell growth , *IMMUNOCYTOCHEMISTRY - Abstract
Abstract: 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 1.46–9.19μM 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. [Copyright &y& Elsevier]
- Published
- 2013
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