The design of cobalt(III) complexes of phenazine-1-carboxamides as prointercalators and potential hypoxia-selective cytotoxins.

Abstract

A series of cobalt (III) complexes, [Co(Racac)2(L)]+, have been prepared as potential hypoxia-selective prointercalator forms of the ligands L, where L is the cytotoxic DNA mono-intercalating ligands N-[2-[(aminoethyl)amino]ethyl]-phenazine-1-carboxamide and N-[5-[(aminoethyl)amino]pentyl]-phenazine-1-carboxamide or the potentially bis(intercalating) ligand bis[2-(phenazine-1-carboxamido)ethyl]-1,2-diaminoethane. The cobalt(III) complexes of the monointercalating ligands have significantly lower DNA binding affinity and cytotoxicity than the ligands themselves, indicating the potential utility of this prodrug approach for deactivation (and release under hypoxic conditions). However, the complexes showed only low hypoxic selectivity. The complex of the bis(intercalating) ligand also showed significantly lower DNA binding affinity than the free ligand, but in this case there was no attenuation of cytotoxicity.

• Authors: L C Perrin, W R Wilson, W A Denny, W D McFadyen
• Journal: Anti-cancer drug design (Anticancer Drug Des) Vol. 14 Issue 3 Pg. 231-41 (Jun 1999) ISSN: 0266-9536 [Print] United States
• PMID: 10500498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Chelating Agents
• Growth Inhibitors
• Intercalating Agents
• Organometallic Compounds
• Phenazines
• Cobalt
• DNA

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
• Chelating Agents (chemistry)
• Cobalt (chemistry, toxicity)
• Cricetinae
• Cricetulus
• DNA (metabolism)
• Electrochemistry
• Growth Inhibitors (chemical synthesis, chemistry, toxicity)
• Hypoxia (metabolism)
• Intercalating Agents (chemical synthesis, chemistry, toxicity)
• Kinetics
• Mice
• Nuclear Magnetic Resonance, Biomolecular
• Organometallic Compounds (chemical synthesis, chemistry, toxicity)
• Phenazines (chemical synthesis, chemistry, toxicity)