著者

寺田 忠史 藤本 勝彦 野村 誠 山下 純一 / 小武内 尚 武田 節夫 南 慶典 吉田 健一郎 山口 秀夫 山田 雄次 Yuji YAMADA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.41, no.5, pp.907-912, 1993-05-15 (Released:2008-03-31)

参考文献数

58

被引用文献数

6 10

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1-β-Alkyl derivatives of 1-desoxypodophyllotoxin were synthesized, and their cytotoxicity and inhibitory effects on DNA topoisomerase II (Topo-II) and tubulin polymerization were examined.The reaction of epipodophyllotoxin derivatives (1a-c) with trimethylallylsilane in the presence of boron trifluoride etherate gave 1-β-allylated compounds (2a-c). The regiochemistry and the β-stereochemistry of the 1-allyl group were confirmed by comparison of the 13C-NMR spectra and NOE's (%) of 2c, podophyllotoxin (POD) and epipodophyllotoxin (1b). 1-β-Alkyl-1-desoxypodophyllotoxin derivatives (3-8) were prepared from 2b.None of the tested compounds (3-8) showed any inhibitory effect on Topo-II. 1-β-Propyl compound (3) and its 4'-demethyl compound (4) inhibited tubulin polymerization and the cytotoxicities of these compounds were equal to that of VP-16. 1-β-(2, 3-Dihydroxypropyl) compounds (5 and 8) and 1-β-(2, 3-diacetoxypropyl) compounds (6 and 7)showed no inhibitory effect on tubulin polymerization. Although 5 did not inhibit either Topo-II activity or tubulin polymerization, it showed a high cytotoxicity against sarcoma 180.