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Pure Appl. Chem. Vol. 73, No. 9, pp. 1393-1400 (2001)

Pure and Applied Chemistry

Vol. 73, Issue 9


Semicarbazide-sensitive amine oxidase. Its physiological significance*

K. Magyar1,#, Z. Mészáros1, and P. Mátyus2

1Department of Pharmacodynamics and 2Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary

Abstract: Although the existence of plasma- and tissue-bound semicarbazide-sensitive amine oxidases (SSAOs) has been recognized earlier, the physiological relevance of the enzyme still remains uncertain. Recent data suggest that elevated serum SSAO activity might cause endothelial injury. Formation of cytotoxic metabolites (e.g., formaldehyde) and increased oxidative stress might lead to initiation or progression of atherosclerosis. Significant positive correlation was found between serum SSAO activity and severity of atherosclerosis, and diabetic macrovascular complications. Effective and selective inhibitors of human SSAO might exert cytoprotective effect on endothelial cells. Compounds, having similar structure to mexiletine, were synthesized and studied relating to SSAO activity. The reference substrate was MDL-72974A. Unfortunately, our new compounds did not reach the potency of the reference substance using human serum samples. In conclusion, we suppose that vascular and soluble SSAO enzymes might have different inhibitor sensitivity. Further studies are required to determine whether the soluble or vascular isoform of SSAO will be the main therapeutic target in the future.

*Plenary lecture presented at the Hungarian-German-Italian-Polish Joint Meeting on Medicinal Chemistry, Budapest, Hungary, 2 –6 September 2001. Other presentations are published in this issue, pp. 1387-1509.
# Corresponding author.

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