Dinitrosyl Iron Complexes with Thiol-Containing Ligands as a Base for New-Generation Drugs (Review)

ABSTRACT

Some present-day concepts of biological activities of dinitrosyl iron complexes (DNIC) with thiol-containing ligands are reviewed. These activities are determined by the ability of DNIC to act as donors of NO and nitrosonium ions (NO+) in various body cells and tissues. DNIC are endowed with strong vasodilator activity. Due to the latter DNIC single dose injection into animal and human organisms induces long-lasting hypotension. Moreover, DNIC suppress platelet aggregation, increase red blood cell elasticity, accelerate skin wound healing, induce penis erection in animals and exert pronounced anti-apoptotic effect on cultured non-tumor cells. These regulatory effects are due to the slow release of NO and NO+ from intact DNIC at both organism and in cell cultures. Fast decomposition of DNIC, e.g., in the presence of exogenous or endogenous iron-chelating agents, results in a toxic effect of DNIC on various cells and tissues and causes apoptosis of, e.g., HeLa and Jurkat human tumor cells. More recent model studies established the ability of DNIC to suppress endometriosis in rats.

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