11-substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents

被引：12

作者：

Feng, Wei ^{[1
]}

Satyanarayana, Mavurapu ^{[1
]}

Tsai, Yuan-Chin ^{[2
]}

Liu, Angela A. ^{[2
]}

Liu, Leroy F. ^{[2
,3
]}

LaVoie, Edmond J. ^{[1
,3
]}

机构：

[1] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut Chem, Piscataway, NJ 08854 USA

[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA

[3] Canc Inst New Jersey, New Brunswick, NJ 08901 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 18期

关键词：

cytotoxicity; antitumor agents; topoisomerase I; benzo[i]phenanthridines; multidrug resistance; photocyclization;

D O I：

10.1016/j.bmc.2008.08.018

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：

Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC50 values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：8598 / 8606

页数：9

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