Details

Autor(en) / Beteiligte

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

Titel

Synthesis and antitumor activity of tropolone derivatives. 6. Structure-activity relationships of antitumor-active tropolone and 8-hydroxyquinoline derivatives

Ist Teil von

• Journal of medicinal chemistry, 1987-10, Vol.30 (10), p.1897-1900

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

1987

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 1b. 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 1a-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.