具有强效靶向拓扑异构酶I活性和细胞毒性的二甲氧基苯并[i]菲啶-12-羧酸衍生物及6H-二苯并[c,h][2,6]萘啶-5-酮

Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity.

作者信息

Ruchelman Alexander L, Zhu Shejin, Zhou Nai, Liu Angela, Liu Leroy F, LaVoie Edmond J

机构信息

Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.

出版信息

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5585-9. doi: 10.1016/j.bmcl.2004.08.070.

DOI:10.1016/j.bmcl.2004.08.070

Abstract

The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12-carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5-ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARC-111.

摘要

ARC-111（1）卓越的靶向TOP1活性和抗肿瘤活性促使人们对类似取代的苯并[i]菲啶-12-羧酸酯和酰胺衍生物展开研究。这些研究进一步拓展至包括6-取代的8,9-二甲氧基-2,3-亚甲基二氧基-二苯并[c,h][2,6]萘啶-5-酮，它们是1的内酰胺反向类似物。这些类似物中有几种保留了ARC-111所具有的强效靶向TOP1活性和细胞毒性。

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