2,3-Dimethoxybenzo[i]phenanthridines: Topoisomerase I-targeting anticancer agents

Dajie Li, Baoping Zhao, Sai Peng Sim, Tsai Kun Li, Angela Liu, Leroy F. Liu, Edmond J. LaVoie

研究成果: 雜誌貢獻文章同行評審

50 引文 斯高帕斯(Scopus)


Appropriately substituted benzo[i]phenanthridines structurally related to nitidine, a benzo[c]phenanthridine alkaloid with antitumor activity, are active as topoisomerase I-targeting agents. Studies on benzo[i]phenanthridines have indicated analogues that possess a 2,3-methylenedioxy moiety and at least one and preferably two methoxyl groups at the 8- and 9-positions, such as 8,9-dimethoxy-2,3-methylenedioxybenzo[i]phenanthridine, 2, are active as topoisomerase I-targeting agents. Tetramethoxylated benzo[i]phenanthridines, wherein the 2,3-methylenedioxy moiety is replaced with methoxyl groups at the 2- and 3-position, are inactive as a topoisomerase I-targeting agent. These results initially suggested that the 2,3-methylenedioxy moiety was critical to the retention of potent activity. Further studies revealed that 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine, 7a, is more potent than 2 as a topoisomerase I-targeting agent. The observation that 2,3-dimethoxylated benzo[i]phenanthridines can actually exhibit enhanced activity prompted the present study in which several 8-substituted 2,3-dimethoxybenzo[i]phenanthridines were prepared and their pharmacological activities evaluated. The influence of NH2, CN, CH2OH, OBn, OCH3, OH, and NHCOCH3substituents at the 8-position on the relative activity of these 2,3-dimethoxybenzo[i]phenanthridines was examined. Relative to these derivatives, 7a was the most potent topoisomerase I-targeting agent, possessing similar cytotoxicity to that of nitidine in the human lymphoblast tumor cell line, RPMI8402.

頁(從 - 到)521-528
期刊Bioorganic and Medicinal Chemistry
出版狀態已發佈 - 2月 2002

ASJC Scopus subject areas

  • 藥物發現
  • 分子醫學
  • 分子生物學
  • 生物化學
  • 臨床生物化學
  • 藥學科學
  • 有機化學


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