Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa

Sphingomyelinase is considered to be involved in the regulation of apoptosi s and cell growth. In the course of our screening for acidic sphingomyelina se inhibitors we isolated three xanthone compounds, alpha-mangostin, cowani n, and cowanol, from the bark of Garcinia speciosa. These compounds competi tively inhibited bovine brain-derived acidic sphingomyelinase with IC50 val ues of 14.1, 19.2, and 10.9 mu M, respectively and inhibited the acidic sph ingomyelinase more effectively than the neutral sphingomyelinase of bovine brain. alpha-Mangostin inhibited the acidic sphingomyelinase in the most se lective manner, alpha-Mangostin was chemically modified and its structure-a ctivity relationships are discussed.