Quantitative structure-activity relationships on 5-substituted terbenzimidazoles as topoisomerase I poisons and antitumor agents

Jung Sun Kim, Qun Sun, Chiang Yu, Angela Liu, Leroy F. Liu, Edmond J. Lavoie

研究成果: 雜誌貢獻文章同行評審

43 引文 斯高帕斯(Scopus)

摘要

Several 5-substituted terbenzimidazoles were synthesized and evaluated as mammalian topoisomerase I poisons and for cytotoxicity against a human lymphoblastoma cell line, RPMI-8402. No correlation was observed between topoisomerase I poisoning activity and the Hansch π value or the σ(meta) and σ(para) values associated with each substituent. These data suggest that electronic effects and relative lipophilicity of substituents at the 5-position of these terbenzimidazoles do not have a significant effect upon intrinsic topoisomerase I poisoning activity. There was, however, a good correlation between the relative π values for the various subtituents evaluated and cytotoxic activity. Experimentally determined log P values did not correlate well with either cytotoxicity or π values. Capacity factors (log k') as determined by high pressure liquid chromatography did correlate well with the π values of varied substituents and cytotoxicity. These data indicate that the relative lipophilic activity of substituents at the 5-position of these terbenzimidazoles can strongly influence relative cytotoxic activity.

原文英語
頁(從 - 到)163-172
頁數10
期刊Bioorganic and Medicinal Chemistry
6
發行號2
DOIs
出版狀態已發佈 - 2月 1 1998
對外發佈

ASJC Scopus subject areas

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

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