Ruthenium as an effective nitric oxide scavenger.
Whilst nitric oxide (NO) has emerged as one of the most versatile and ubiquitous molecules in the human body with a diverse range of physiological functions, dysfunction in NO biosynthesis or metabolism has led to the pathogenesis of a number of disease states. A variety of therapeutic strategies have therefore emerged that either reduce or increase endogenous NO levels depending on the disease pathology. The predominant strategy to date to reduce levels of NO is to utilise specific isoform selective inhibitors of nitric oxide synthases, the enzymes responsible for NO biosynthesis. An alternative line of attack, not related to specificity for a particular enzyme, but rather on compartmental localisation and pharmacokinetics, is to remove or scavenge the excess NO responsible for the disease pathology. In this regard, a number of NO scavenger molecules have demonstrated pharmacological activity across a broad spectrum of disease states. This review will highlight the rationale behind the development, and the current state of play, of one such class of NO scavengers, complexes of the d-block transition metal ruthenium. Prior to this, a brief overview of the remarkable diversity of NO, both from a chemical and biological viewpoint, will be provided for perspective.
Marmion
Celine J
CJ
Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland. cmarmion@rcsi.ie
Cameron
Beth
B
Mulcahy
Clodagh
C
Fricker
Simon P
SP
D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012428:Ruthenium / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D009569:Nitric Oxide; D012428:Ruthenium