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 bindi ng 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 capil laris Flos (''Inchinko'' in Japanese), which has been utilized as a re medy for hepatitis in Oriental medicine. In receptor binding experimen ts, compound 1 inhibited ET-1 binding specifically to both the ET(A) r eceptor (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 bi nding inhibitor; however, it exhibited no affinity for the other recep tors of angiotensin IT and atrial natriuretic peptide. We also evaluat ed the inhibitory activity of porphyrin compounds, and found that some exhibited moderate activity.