Synthesis and antitumor activity of tropolone derivatives. 7. Bistropolones containing connecting methylene chains.

Abstract

Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme.

• Authors: M Yamato, J Ando, K Sakaki, K Hashigaki, Y Wataya, S Tsukagoshi, T Tashiro, T Tsuruo
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 35 Issue 2 Pg. 267-73 (Jan 24 1992) ISSN: 0022-2623 [Print] United States
• PMID: 1732542 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Deoxyribonucleotides
• Tropolone

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Deoxyribonucleotides (metabolism)
• Leukemia P388 (drug therapy)
• Mice
• Structure-Activity Relationship
• Tropolone (analogs & derivatives, chemical synthesis, pharmacology)
• Tumor Cells, Cultured (drug effects)