Synthesis and cytotoxic activity of pyrazino[1,2-b]-isoquinolines, 1-(3-isoquinolyl)isoquinolines, and 6,15-iminoisoquino-[3,2-b]-3-benzazocines

被引：55

作者：

Gonzalez, Juan Francisco ^{[1
]}

de la Cuesta, Elena ^{[1
]}

Avendano, Carmen ^{[1
]}

机构：

[1] Univ Complutense Madrid, Fac Farm, Dept Quim Organ & Farmaceut, E-28040 Madrid, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 01期

关键词：

antitumor agents; tetrahydroisoquinolines; cribrostatin; 4; phthalascidin; acyliminium cations;

D O I：

10.1016/j.bmc.2006.10.009

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 pyrazino[2,1-b]isoquinoline and 6,15-iminoisoquino[3,2-b]-3-benzazocine compounds related to renieramyeins, cribrostatin 4, and phthalascidin was synthesized and their in vitro cytotoxic activities were evaluated against three human cancer cell lines. Pyrazino[2,1-b]isoquinolines, 6,15-iminoisoquino[3,2-b]-3-benzazocines, and other more complex octacyclic compounds have been obtained and derived to precursors of iminium ion species. Hydrogenolysis of the lactam function in pentacyclic compounds gave 1-(3-isoquinolyl)isoquinolines. The micromolar cytotoxic activity of representative structures was apparently uninfluenced by the ability to generate intermediates which would permit covalent bonding to DNA. (c) 2006 Published by Elsevier Ltd.

引用

页码：112 / 118

页数：7

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