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-Fong Liu, Edmond J. Lavoie

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40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume6
Issue number2
DOIs
Publication statusPublished - Feb 1 1998
Externally publishedYes

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Keywords

  • Antitumor
  • QSAR
  • Structure-activity
  • Terbenzimidazoles
  • Topoisomerase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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