具有异戊二烯衍生侧链的外消旋异去氧鬼臼毒素类似物的合成与细胞毒性

Synthesis and cytotoxicity of racemic isodeoxypodophyllotoxin analogues with isoprene-derived side chains.

作者信息

Zhao Yu, Feng Ju Hong, Ding Hong Xia, Xiong Yi, Cheng Christopher H K, Hao Xiao Jiang, Zhang Yong Min, Pan Yuan Jiang, Guéritte Françoise, Wu Xiu Mei, Bai Hua, Stöckigt Joachim

机构信息

Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Yan An Road 353, Hangzhou 310031, People's Republic of China.

出版信息

J Nat Prod. 2006 Aug;69(8):1145-52. doi: 10.1021/np050547x.

DOI:10.1021/np050547x

PMID:16933865

Abstract

A series of isodeoxypodophyllotoxin (5) analogues, 26-38, with various isoprene-derived side chains at the E-ring were designed and synthesized. For comparison, compound 39, with a benzyloxy group on the E-ring, and six D-ring opened analogues, 40-45, were also prepared. All the synthetic compounds were evaluated for their cytotoxic activities in vitro against seven cultured human tumor cell lines. Compounds 27, 43, and 44 were more cytotoxic than etoposide on BEL-7404, A549, and HL-60 cell lines, respectively. However, none of the synthetic isodeoxypodophyllotoxins were more cytotoxic than podophyllotoxin (1).

摘要

设计并合成了一系列异去氧鬼臼毒素（5）类似物（26 - 38），其E环带有各种异戊二烯衍生的侧链。为作比较，还制备了E环带有苄氧基的化合物39以及六个D环开环类似物（40 - 45）。对所有合成化合物进行了体外抗七种培养的人肿瘤细胞系的细胞毒性活性评估。化合物27、43和44在BEL - 7404、A549和HL - 60细胞系上分别比依托泊苷具有更强的细胞毒性。然而，合成的异去氧鬼臼毒素均不比鬼臼毒素（1）的细胞毒性更强。