Discovery of novel andrographolide derivatives as cytotoxic agents |
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| Authors: | Shanfu Wei Yan-Bo Tang Huiming Hua Emika Ohkoshi Masuo Goto Li-Ting Wang Kuo-Hsiung Lee Zhiyan Xiao |
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| Institution: | 1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China;2. Key Laboratory of Structure-Based Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;3. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, United States;4. Chinese Medicine Research and Development Center, China Medical University & Hospital, Taichung, Taiwan |
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| 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 1.46–9.19 μM 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. |
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| Keywords: | Andrographolide derivatives Labdane diterpenes Cytotoxicity Microtubule dynamics |
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