Abstract
l,3-Dihydroxy-2-methylxanthone (XI), its 4-chloro and 4-bromo derivatives (X1-C1 and Xl-Br), and 1 ,3-dihydroxy-4-methylxanthone were investigated for their inhibition activities toward MAO. A hyperbolic function was derived to fit the data and to calculate IC50 values. The compounds proved to be reversible and selective inhibitors of MAO-A, with XI displaying the highest activity (IC50 = 3.7 µM).
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REFERENCES
M. Strolin-Benedetti and P. Dostert. Monoamine oxidase: From physiology and pathophysiology to the design and clinical application of reversible inhibitors. In B. Testa (ed.), Advances in Drug Research, Academic Press, London, 1992, Vol. 23, pp. 65–125.
E. Kyburz. New developments in the field of MAO-inhibitors. Drug News Persp. 3:592–599 (1990).
Y. P. Hsu, J. S. Powell, K. B. Sims, and X. Breakefield. Molecular genetics of the monoamine oxidase. J. Neurochem. 53:12–18 (1989).
O. Suzuki, Y. Katsumata, M. Oya, V. M. Chari, R. Klapfenberger, H. Wagner, and K. Hostettmann. Inhibition of type A and type B monoamine oxidase by isogentisin and its 3-O-glucoside. Planta Med. 39:19–23 (1980).
O. Suzuki, Y. Katsumata, M. Oya, V. M. Chari, B. Vermes, H. Wagner, and K. Hostettmann. Inhibition of type A and type B monoamine oxidase by naturally occuring xanthones. Planta Med. 42:17–21 (1981).
D. Schaufelberger and K. Hostettmann. Chemistry and pharmacology of Gentiana lactea, Planta Med. 54:219–221 (1987).
M. M. Pinto and J. Polonia. Synthesis of new xanthones, I. Helv. Chim. Acta 57:2613–2617 (1974).
F. Borges and M. Pinto. Synthesis of coumarins and derivatives. I. Biomimetic synthesis of esculetin and halogenated derivatives. Helv. Chim. Acta 75:1061–1068 (1992).
J. B. Clark and W. J. Nicklas. The metabolism of rat brain mitochondria: Preparation and characterization. J. Biol. Chem. 245:4724–4731 (1970).
B. Walther, J. F. Ghersi-Egea, Z. Jayyosi, A. Minn, and G. Siest. Ethoxyresorufin-O-deethylase activity in rat brain subcellular fractions. Neurosci. Lett. 76:58–62 (1987).
O. H. Lowry, N. J. Rosebrough, L. Farr, and R. J. Ran. Protein measurement with the Folin phenol agent. J. Biol. Chem. 193:265–275 (1951).
H. Weissbach, T. E. Smith, J. W. Daly, B. Witkop, and S. Udenfriend. A rapid spectrophotometric assay of monoamine oxidase based on the rate of disappearance of kynuramine. J. Biol. Chem. 235:1160–1163 (1960).
P. Henderson. Statistical analysis of enzyme kinetic data. In K. F. Tipton (ed.), Techniques in the Life Sciences, Protein and Enzyme Biochemistry B1/2 (Suppl.), 1985, pp. 1–48.
K. F. Tipton and C. J. Fowler. The kinetics of monoamine oxidase inhibitors in relation to their clinical behaviour. In K. F. Tipton, P. Dostert, and M. Strolin-Benedetti (eds.), Monoamine Oxidase and Disease, Academic Press, London, 1984, pp. 27–40.
P. C. Engel. Enzyme kinetics. In M. I. Page (ed.), The Chemistry of Enzyme Action, Elsevier, Amsterdam, 1984, pp. 73–110.
Y.-C. Cheng and W. H. Prusoff. Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 22:3099–3108 (1973).
W. Haefely, W. P. Burkard, A. M. Cesura, R. Kettler, H. P. Lorez, J. R. Martin, J. G. Richards, R. Scherschlicht, and M. Da Prada. Biochemistry and pharmacology of moclobemide, a prototype RIMA. Psychopharmacology 106:6–14 (1992).
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Thull, U., Kneubühler, S., Testa, B. et al. Substituted Xanthones as Selective and Reversible Monoamine Oxidase A (MAO-A) Inhibitors. Pharm Res 10, 1187–1190 (1993). https://doi.org/10.1023/A:1018924503552
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DOI: https://doi.org/10.1023/A:1018924503552