PHEOPHORBIDE A, A POTENT ENDOTHELIN RECEPTOR ANTAGONIST FOR BOTH ET(A) AND ET(B) SUBTYPES

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(A)R) and ET(B) receptor (ET(B)R), with IC50 values of 8.0 x 10(-8) and 2.1x10(-7)M, respectively. Thus, compound 1 is an ET-1 binding inhibitor; however, it exhibited no affinity for the other receptors of angiotensin IT and atrial natriuretic peptide. We also evaluated the inhibitory activity of porphyrin compounds, and found that some exhibited moderate activity.