Pheophorbide a, a Potent Endothelin Receptor Antagonist for Both ET_A and ET_B Subtypes

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 ET_A receptor (ET_AR) and ET_B receptor (ET_BR), with IC₅₀ values of 8.0×10^-8 and 2.1×10^-7M, respectively. Thus, compound 1 is an ET-1 binding inhibitor; howver, 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.