DINITROSYL IRON COMPLEXES WITH THIOL-CONTAINING LIGANDS AS A BASE FOR NEW-GENERATION DRUGS
Anatoly F. Vanin
Semenov Institute of Chemical Physics, Russian Academy of Science, Moscow, Russian Federation
Dinitrosyl iron complexes (DNIC) with thiol-containing ligands, which fulfil the function of nitrogen monoxide and nitrosonium ion donors, hold considerable promise as a base in the design of new-generation drugs endowed with a broad spectrum of therapeutic activities. In particular, DNIC with glutathione were recently used as a base for a novel stable hypotensive drug Oxacom; its pharmacological trials demonstrated its high hypotensive activity. Thus, single intravenous infusion of an Oxacom solution (0.2 µmol of active substance/kg body weight) induced a 20-30% drop of arterial pressure, which lasted from 6 to 8 h. Animal studies based on a similar protocol established that aqueous solutions of DNIC with glutathione or cysteine may also exert long-lasting hypotensive effect upon intravenous and intramuscular, subcutaneous or intraperitoneal administration. In addition, DNIC accelerate skin wound healing, exert enhanced penile erective effect and prevent experimental endometriosis in rats. The data obtained suggest that DNIC with thiol-containing ligands being decomposed manifest strong cytotoxic activity against pathogenic bacteria, mycobacteria and malignantly transformed cells.