RES-1149-1 and -2, novel non-peptidic endothelin type B receptor antagonists produced by Aspergillus sp. III. Biochemical properties of RES-1149-1, -2 and structure-activity relationships

Abstract

RES-1149-1 and -2, produced by Aspergillus sp. RE-1149, were found to be non-peptidic antagonists for endothelin type B receptor (ET(B) receptor). RES-1149-1 and -2 selectively inhibited the endothelin-1 (ET-1) binding to ET(B) receptor in a competitive manner with IC50 values of 1.5 μM and 20 μM, respectively. RES-1149-1 inhibited the increase in intracellular Ca2+ concentration elicited by 1 nM ET-1 in COS-7 cells expressing human ET(B) receptor, but not in the case of cells expressing ET(A) receptor. In addition, some structure-activity relationships are described.