title: 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 from a higher plant, a new triterpenoid, myriceric 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 Ca2+ concentration (IC50 = 11 +/- 2 nM) but [125I]endothelin-1 binding in rat aortic smooth muscle cells (Ki = 66 +/- 15 nM). 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 derivatives (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.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakurawi
authors.forename: F
authors.initials: F
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Tozyo
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: J
authors.initials: J
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Terui
authors.forename: Y
authors.initials: Y
authors.lastname: Ikenishi
authors.forename: T
authors.initials: T
authors.lastname: Iwata
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Konoike
authors.forename: S
authors.initials: S
authors.lastname: Mihara
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D014315:Triterpenes; C102847:myriceric acid A; D002118:Calcium