Pheophorbide a, a potent endothelin receptor antagonist for both ETA and ETB subtypes

Chem Pharm Bull (Tokyo). 1994 Oct;42(10):2174-6. doi: 10.1248/cpb.42.2174.

Abstract

Many crude drugs were screened for their capacity to inhibit the binding of endothelin-1 (ET-1) to ET receptors; several crude drugs showed significant binding inhibitory activity. Pheophorbide a (1), a potent non-peptide ET receptor antagonist, was isolated from Altemisiae capillaris Flos ("Inchinko" in Japanese), which has been utilized as a remedy for hepatitis in Oriental medicine. In receptor binding experiments, compound 1 inhibited ET-1 binding specifically to both the ETA receptor (ETAR) and ETB receptor (ETBR), with IC50 values of 8.0 x 10(-8) and 2.1 x 10(-7) M, respectively. Thus, compound 1 is an ET-1 binding inhibitor; however, it exhibited no affinity for the other receptors of angiotensin II and atrial natriuretic peptide. We also evaluated the inhibitory activity of porphyrin compounds, and found that some exhibited moderate activity.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / chemistry
  • Chlorophyll / isolation & purification
  • Chlorophyll / pharmacology
  • Endothelin Receptor Antagonists*
  • Japan
  • Medicine, East Asian Traditional
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Swine

Substances

  • Endothelin Receptor Antagonists
  • Plant Extracts
  • Chlorophyll
  • pheophorbide a