Tomio Ogasawara

Xanthone derivatives as inhibitors for monoamine oxidase

Abstract Various xanthone derivatives were tested for in vitro inhibition of monoamine oxidase (MAO) in the mitochondrial fraction from rat brain and mouse liver. 1,6-Dihydroxyxanthone and 1,3,6-trihydroxyxanthone exhibited much potent inhibitory activity toward rat brain mitochondrial MAO (type A). On the other hand, 1,3,7-trihydroxyxanthone showed great potency for inhibition of mouse liver mitochondrial MAO (type B). These results indicate that 1,3,6-trihydroxyxanthone and 1,3,7-trihydroxyxanthone were rather specific inhibitors of type A MAO and type B MAO, respectively. 1,3-Dihydroxy-6-alkoxyxanthones containing alkoxy residues with carbon number 1 to 8 were synthesized and compared for their inhibitory activity toward rat brain mitochondrial MAO. Among them, 6-ethoxy-, 6-propyloxy-, and 6-butyloxy-derivatives were potent inhibitors, and especially, 1,3-dihydroxy-6-propyloxyxanthone was the most inhibitory. Lineweaver–Burk plot analysis demonstrates that these xanthone derivatives inhibited MAO in a competitive and reversible manner. Spectroscopic examinations suggest that complex formation between the flavin moiety and a xanthone derivative could be involved at least partly in their inhibitory action.