Journal
JOURNAL OF ANTIBIOTICS
Volume 62, Issue 7, Pages 359-364Publisher
JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2009.40
Keywords
Ascotricha chartarum; ascotricins A and B; HUVEC; S1P(1) antagonist; sphingosine-1-phosphate
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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 mu m, respectively. In a [(33)P]sphingosine-1-phosphate/S1P(1)-binding assay, those values were 120 and 39 mu m, and in a migration assay using human umbilical vein endothelial cells (HUVECs), they were 94 and 28 mu m, respectively. Thus, ascotricins A and B are novel S1P(1) antagonists showing an inhibition activity toward HUVEC migration. The Journal of Antibiotics (2009) 62, 359-364; doi:10.1038/ja.2009.40; published online 22 May 2009
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