Progress towards the discovery of xanthine oxidase inhibitors

• Tipo: Artigo em Revista Científica Internacional
• Data: 2002

Autores

Borges, F (Autor) FFUP; Fernandes, E (Autor) FFUP; Roleira, F (Autor) Outra

Revista

Título: Current Medicinal Chemistry

Vol. 9

Páginas: 195-217

ISSN: 0929-8673

Editora: Bentham Science

Indexação

ISI Web of Knowledge - 301 Citações

Scopus - 325 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

CORDIS: Ciências Físicas > Química > Química aplicada > Química farmacêutica

Outras Informações

ID Authenticus: P-000-R19

Abstract (EN): Xanthine oxidase (XO) is a highly versatile flavoprotein enzyme, ubiquitous among species (from bacteria to human) and within the various tissues of. mammals. The enzyme catalyses the oxidative hydroxylation of purine substrates at the molybdenum centre (the reductive half-reaction) and subsequent reduction Of O-2 at the flavin centre with generation of reactive oxygen species (ROS), either superoxide anion radical or hydrogen peroxide (the oxidative half-reaction). Many diseases, or at least symptoms of diseases, arise from a deficiency or excess of a specific metabolite in the body. For an example of an excess of a particular metabolite that produces a disease state is the excess of uric acid which can led to gout. Inhibition of XO decreases the uric acid levels, and results in an antihyperuricemic effect. Allopurinol, first synthesised as a potential anticancer agent, is nowadays a clinically useful xanthine oxidase inhibitor used in the treatment of gout. There is overwhelming acceptance that xanthine oxidase serum levels are significantly increased in various pathological states like hepatitis, inflammation, ischemia-reperfusion, carcinogenesis and aging and that ROS generated in the enzymatic process are involved in oxidative damage. Thus, it may be possible that the inhibition of this enzymatic pathway would be beneficial. In this review the State of the Art will be presented, which includes a summary of the progress made over the past years in the knowledge of the structure and mechanism of the enzyme, associated pathological states, and in the efforts made towards the development of new xanthine oxidase inhibitors.

Idioma: Inglês

Tipo (Avaliação Docente): Científica