2,9-Dimethyl-1,10-phenanthroline (neocuproine): a potent, copper-dependent cytotoxin with anti-tumor activity.

Abstract

2,9-Dimethyl-1,10-phenanthroline (2,9-DMP), a copper-specific chelator, was a potent cytotoxin against L1210 cells in vitro; its activity was dependent upon available Cu2+ in the medium. Other divalent ions, Fe2+ and Zn2+, were ineffective as promoters of growth inhibition. As the copper chelate, a 4 microM solution produced a 4 log kill after a 1-hr incubation. This was in marked contrast to 1,10-phenanthroline, whose inhibition of cell growth was overcome by added Cu2+, Fe2+ and Zn2+. Cellular uptake of labeled 2,9-dimethyl-1,10-phenanthroline also required added Cu2+ in the medium. This transport was energy dependent, and the drug was concentrated over 200-fold by the cells. In preliminary evaluations, copper-2,9-DMP showed significant chemotherapeutic activity against the P388 murine lymphoma in vivo.

• Authors: A Mohindru, J M Fisher, M Rabinovitz
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 32 Issue 23 Pg. 3627-32 (Dec 01 1983) ISSN: 0006-2952 [Print] England
• PMID: 6651879 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Phenanthrolines
• Copper
• neocuproine

Topics

• Animals
• Antineoplastic Agents
• Biological Transport
• Cell Line
• Cell Survival (drug effects)
• Copper (metabolism, pharmacology)
• Leukemia L1210 (drug therapy)
• Leukemia P388 (drug therapy)
• Male
• Mice
• Phenanthrolines (metabolism, pharmacology)