RES-1214-1 and -2, Novel Non-peptidic Endothelin Type A Receptor Antagonists Produced by Pestalotiopsis sp.

Abstract

RES-1214-1 and -2, novel and non-peptidic endothelin antagonists, were isolated from the cultured broth of a fungus, Pestalotiopsis sp. RE-1214. RES-1214-1 and -2 selectivity inhibited the ET-1 binding to endothelin type A receptor (ETA receptor) with IC50 values of 1.5 microM and 10 microM, respectively. RES-1214-1 and -2 inhibited the increase in intracellular Ca2+ concentration elicited by 1 nM ET-1 in A10 cells. Taxonomy of producing strains, fermentation, isolation, structural determination, and biochemical properties of RES-1214-1 and-2 are described.