Synthesis and antitumor activity of duocarmycin derivatives:: A-ring pyrrole compounds bearing (β-(5′,6′,7′-trimethoxy-2′-indolyl)acryloyl group

被引:24
作者
Amishiro, N [1 ]
Nagamura, S [1 ]
Kobayashi, E [1 ]
Okamoto, A [1 ]
Gomi, K [1 ]
Okabe, M [1 ]
Saito, H [1 ]
机构
[1] Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Nagaizumi, Shizuoka 4118731, Japan
关键词
D O I
10.1016/S0968-0896(00)00086-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of A-ring pyrrole derivatives of duocarmycin bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group were synthesized, and evaluated for in vitro anticellular activity against HeLa Sg cells and in vivo antitumor activity against murine sarcoma 180 in mice. New Seg-B analogues bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group containing double bond as spacer had lower peripheral blood toxicity than the derivatives bearing S',6',7'-trimethoxyindole-2'-carboxyl group in Seg-B of the natural type. Moreover, most of them exhibited potent antitumor activity against in vivo murine tumor models. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1637 / 1643
页数:7
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