Ascotricins A and B, novel antagonists of sphingosine-1-phosphate receptor 1 from ascotricha chartarum berk. SANK 14186

Abstract

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 M, respectively. In a 33 Psphingosine-1-phosphate/S1P 1-binding assay, those values were 120 and 39 M, and in a migration assay using human umbilical vein endothelial cells (HUVECs), they were 94 and 28 M, respectively. Thus, ascotricins A and B are novel S1P 1 antagonists showing an inhibition activity toward HUVEC migration. © 2009 Japan Antibiotics Research Association.