Redox-active cobalt complexes as promising antitumor agents

Author： Osinsky S. P. Levitin I. Ya. Sigan A. L. Bubnovskaya L. N. Ganusevich I. I. Campanella L. Wardman P.

ISSN： 1066-5285

Source： Russian Chemical Bulletin, Vol.52, Iss.12, 2003-12, pp. : 2636-2645

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Abstract

Cobalt(iii) complexes with tetradentate aliphatic Schiff"s bases containing also compounds of the vitamin PP series or their analogs as axial ligands were synthesized as potential antitumor agents. The behavior of these redox-active complexes in chemical processes that presumably govern their biological action was studied. These processes include aquation and subsequent decomposition, electrode and homogeneous redox reactions, and catalytic activity in autooxidation of biosubstrates, especially at the stages of generation and consumption of reactive oxygen species (ROS). The antitumor action of these complexes in vivo was studied. Changes in the organisms of laboratory animals characteristic of processes involving ROS were followed at the cellular and molecular levels. The tumor-selective action of the complexes is due to specific features of microenvironment of tumor cells. Some of them exhibit a strong antimetastatic effect, which exceeds that for a number of drugs used in clinical practice. A complex with nicotinamide was recommended for preclinical studies. The scope of application of the redox-active transition metal complexes in oncology is discussed.