Synthesis and Antitumor Activity of Tropolone Derivatives. 6. Structure-Activity Relationships of Antitumor-Active Tropolone and 8-Hydroxyquinoline Derivatives

Masatoshi Yamato, Kuniko Hashigaki, Shigeru Tsukagoshi, Tazuko Tashiro, Takashi Tsuruo, Yoshiko Yasumoto, Junko Sakai, Richard F. Luduena, Asok Banerjee

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The bis derivative 6 of 8-hydroxyquinoline, which, like tropolones, readily forms a chelate, was synthesized and found to have high potency (dose = 12.5 mg/kg, T/C % = 164) against leukemia P388 in mice approximately equivalent to that of the bistropolone lb. 8-Hydroxyquinoline analogues with broad structural variation were synthesized and their structure-activity relationships followed the same pattern as in the tropolone series. In addition, the bistropolones la-e were tested for their ability to bind to tubulin and found to have no such property. The results of this study suggested that bistropolone and bis(8-hydroxyquinoline) derivatives must form a chelate with the metal necessary for the enzyme, such as ribonucleotide reductase, which catalyzes the DNA biosynthetic pathways.

Original languageEnglish (US)
Pages (from-to)1897-1900
Number of pages4
JournalJournal of Medicinal Chemistry
Volume30
Issue number10
DOIs
StatePublished - Oct 1 1987

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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