Satyanarayana Mavurapu, Feng Wei, Cheng Liang, Liu Angela A, Tsai Yuan-Chin, Liu Leroy F, LaVoie Edmond J
Department of Pharmaceutical Chemistry, Rutgers, Ernest Mario School of Pharmacy, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
Bioorg Med Chem. 2008 Aug 15;16(16):7824-31. doi: 10.1016/j.bmc.2008.06.046. Epub 2008 Jun 26.
Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.
几种在乙基取代基上具有不同官能团的11-乙基-2,3-二甲氧基-8,9-亚甲基二氧基-11H-异喹啉并[4,3-c]肉桂啉-12-酮表现出强大的靶向拓扑异构酶I（TOP1）活性和抗肿瘤活性。评估了11-乙基取代基2-位上各种极性取代基，包括N-甲胺、N-异丙胺、羟基和羟氨基对TOP1靶向活性和细胞毒性的影响。N-甲胺和N-异丙胺衍生物也作为抗肿瘤剂在具有MDA-MB-435人肿瘤异种移植的无胸腺裸鼠中进行了评估。两种化合物经肠胃外或口服给药后均具有抗肿瘤活性。
