Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa.
Sphingomyelinase is considered to be involved in the regulation of apoptosis and cell growth. In the course of our screening for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, alpha-mangostin, cowanin, and cowanol, from the bark of Garcinia speciosa. These compounds competitively inhibited bovine brain-derived acidic sphingomyelinase with IC(50) values of 14.1, 19.2, and 10.9 microM, respectively and inhibited the acidic sphingomyelinase more effectively than the neutral sphingomyelinase of bovine brain. alpha-Mangostin inhibited the acidic sphingomyelinase in the most selective manner. alpha-Mangostin was chemically modified and its structure-activity relationships are discussed.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan.
C
C
Okudaira
Y
Y
Ikeda
S
S
Kondo
S
S
Furuya
Y
Y
Hirabayashi
T
T
Koyano
Y
Y
Saito
K
K
Umezawa
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D002417:Cattle; D029760:Garcinia / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D013109:Sphingomyelins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
C041065:N-4-nitrobenzo-2-oxa-1,3-diazoleaminocaproyl sphingosylphosphorylcholine; D047428:Protein Kinase Inhibitors; D013109:Sphingomyelins; D014966:Xanthenes; D044004:Xanthones; D013108:Sphingomyelin Phosphodiesterase; D009327:4-Chloro-7-nitrobenzofurazan; C021053:mangostin