Synthesis and cytotoxic activity of N-[(alkylamino)alkyl]-carboxamide derivatives of 7-oxo-7H-benz[de]anthracene, 7-oxo-7H-naphtho[1,2,3-de]quinoline, and 7-oxo-7H-benzo[e]perimidine

被引：24

作者：

Bu, XY ^{[1
]}

Chen, JJ ^{[1
]}

Deady, LW ^{[1
]}

Smith, CL ^{[1
]}

Baguley, BC ^{[1
]}

Greenhalgh, D ^{[1
]}

Yang, SJ ^{[1
]}

Denny, WA ^{[1
]}

机构：

[1] Univ Auckland, Sch Med Sci, Auckland Canc Soc, Res Ctr, Auckland 1000, New Zealand

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 11期

关键词：

naphthoquinolines; GC-selectivity; cytotoxicity; colon; 38; tumors;

D O I：

10.1016/j.bmc.2005.03.033

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：

7-Oxo-7H-naphtho[1,2,3-de]quinoline-11-carboxamides and analogues were prepared and evaluated for in vitro and in vivo antitumor activity. Chromophore variations included 'deaza' (7-oxo-7H-benz[de]anthracene) and 'diaza' (7-oxo-7H-benzo[e]perimidine) analogues, and side chain variations included chiral a-methyl compounds. The naphthoquinolines were the most cytotoxic, with IC50 values of 5-20 nM, and showed the strongest DNA binding, with high selectivity for G-C rich DNA. The chiral a-methyl analogues were 10-20-fold more cytotoxic than the parent des-methyl compound. Both enantiomers provided substantial growth delays against s.c. colon 38 tumors in mice, with the R-enantiomer more active than the S (tumor growth delays of >35 and 12 days, respectively). 2005 Elsevier Ltd. All rights reserved.

引用

页码：3657 / 3665

页数：9

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