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.