Ascotricins A and B, novel antagonists of sphingosine-1-phosphate receptor 1 from Ascotricha chartarum Berk. SANK 14186.
Ascotricins A and B were isolated as novel sphingosine-1-phosphate receptor 1 (S1P(1)) antagonists from a cultured broth of a fungus identified as Ascotricha chartarum Berk. SANK 14186. The two compounds were purified by solvent extraction, reversed-phase (RP) column chromatography and a preparative RP-HPLC. The structures were determined by various NMR experiments and by LC/MS and GC/MS analyses. The S1P(1) antagonist activities were measured by a cyclic AMP assay using S1P(1)-expressing cells and the IC(50) values were 8.2 and 1.8 microM, respectively. In a [(33)P]sphingosine-1-phosphate/S1P(1)-binding assay, those values were 120 and 39 microM, and in a migration assay using human umbilical vein endothelial cells (HUVECs), they were 94 and 28 microM, respectively. Thus, ascotricins A and B are novel S1P(1) antagonists showing an inhibition activity toward HUVEC migration.
Yonesu
Kiyoaki
K
Exploratory Research Laboratories II, Daiichi Sankyo Co. Ltd., Kitakasai, Edogawa-ku, Tokyo, Japan. yonesu.kiyoaki.t8@daiichisankyo.co.jp
Ohnuki
Takashi
T
Ono
Yasunori
Y
Takatsu
Toshio
T
Nara
Futoshi
F
D001203:Ascomycota / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005285:Fermentation; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification
D049349:Receptors, Lysosphingolipid; C544343:ascotricin A; C544344:ascotricin B; D000242:Cyclic AMP; D013110:Sphingosine