Endothelin Receptor Antagonist Triterpenoid, Myriceric Acid A, Isolated from Myrica cerifera, and Structure Activity Relationships of Its Derivatives

Abstract

As the first non-peptide endothelin receptor antagonist form a higher plant, a new triter penoid, myiceric acid A (50-235) (1) was isolated from the bayberry, Myrica cerifera. myriceric acid A (1) inhibited not only an endothelin-1-induced increase in cytosolic free Ca^&amp;glt;2+> concentration (IC₅₀=11±2nM) but [^<125&t;I]endothelin-1 binding in rat aortic smooth muscle cells (K_i=66±15nM). Two new related triterpenoids, myriceric acid C (6), and myriceric acid D (8), were also isolated. Furthermore, the chemical modification of these natural products led to the synthesis of sulfated derivative (13, 14, 15) which showed 1.5 to 20 times higher affinity for endothelin receptors. The structure activity relationships of myriceric acids and their derivatives are discussed.