3-Substituted-4-methoxy-5-hydroxybenzaldehydes and benzoic acids as inhibitors of catechol-O-methyltransferase
The extraneuronal inactivation of catecholamines and the detoxification of many xenobiotic catechols are dependent upon the enzyme catechol-O-methyltransferase (COMT, EC 18.104.22.168). COMT is a soluble, magnesium-requiring enzyme which catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to a catechol substrate resulting in the formation of the meta and para-O-methylated products (Borchardt, 1980).
KeywordsBenzoic Acid Sulfhydryl Group COMT Activity Benzaldehyde Derivative Catechol Substrate
Unable to display preview. Download preview PDF.
- Borchardt, R. T., Cheng, C. F. and Thakker, D. R. (1975). Purification of Catechol-O-Methyltransferase by Affinity Chromatography. Biochem. Biophys. Res. Commun., 63, 69–77.Google Scholar
- Borchardt, R. T. and Thakker, D. R. (1976). Evidence for Sulfhydryl Groups at the Active Site of Catechol-O-Methyltransferase. Biochim. Biophys. Acta, 445, 498–509.Google Scholar
- Borchardt, R. T. (1977). Chemical Probes of the Active Site of Catechol-O-Methyltransferase. In Biochemistry and Function of Monoamine Enzymes, (ed., E. Usdin and N. Weiner), Marcel Dekker, New York, p. 707–720.Google Scholar
- Borchardt, R. T. (1980). N- and O-Methylation. In Enzymatic Basis of Detoxication, Vol. II, Wiley, New York, p. 43–62.Google Scholar
- Borchardt, R. T. (1981). Catechol-O-Methyltransferase: Assay, Purification and Properties. In Methods in Enzymology - Detoxication and Drug Metabolism: Conjugation and Related Systems, (ed., W. B. Jakoby), Academic Press, New York, in press.Google Scholar
- Guldberg, H. C. and Marsden, C. A. (1975). Catechol-O-Methyltransferase: Pharmacological Aspects and Physioloqical Role. Pharmacol. Rev., 27, 135–206.Google Scholar
- Lutz, W. B., Creveling, C. R., Daly, J. W. and Witkop, B. (1972). Sulfur Analogs of Dopamine and Norepinephrine. Inhibition of Catechol-O-Methyltransferase. J. Med. Chem., 15, 795–802.Google Scholar
- Nikodejevic, B., Senoh, S., Daly, J. W. and Creveling, C. R. (1970). Catechol-O-Methyltransferase. II. A New Class of Inhibitors of Catechol-O-Methyltransferase; 3,5-Dihydroxy-4-Methoxybenzoic Acid and Related Compounds. J. Pharmacol. Exptl. Therap., 174, 83–93.Google Scholar