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那可丁衍生物合成及作为微管干扰药物的生物学评估.pdf

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药学学报 Acta Pharmaceutica Sinica 20 12, 47 ( 10): 1347 1357 ·1347 · ·研究论文· Synthesis and biological evaluation of noscapine analogues as microtubule-interfering agents 1 1* 1 1 2 DAI Hou-ling , ZHENG Jian-bin , LIN Min , ZHENG Jing , ZHOU Fu-sheng , 2 1 1 1,2 DONG Xiao-chun , GUO Lei , LIU Jian-wen , WEN Ren (1. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 20023 7, China; 2. School of Pharmacy, Fudan University, Shanghai 201203, China) Abstract: A series of noscapine analogues have been synthesized via 13-step reaction starting from 2- hydroxy-3-methoxybenzaldehyde. Anti-tumor activities of these compounds were evaluated against HL-60 cell lines in vitro by the standard MTT assay. It was found that most of these derivatives showed appreciable inhibitory activity against HL-60 and tubulin polymerization. The results also indicated that the potency of compound 31 is about three times more than that of noscapine against HL-60 cell line and tubulin polymerization. Moreover, it induced a massive accumulation of cells in G /M phase. These results showed noscapine and its 2 derivatives were worth to be intensively studied further. Key words: noscapine; tubulin; cytotoxic activity; microtubule-interfering agent CLC number: R9 16 Document code: A Article ID : 05 13-4870 (20 12) 10- 1347-11