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

• Authors: T Ohshima, M Hirata, T Oda, A Sasaki, M Shiratsuchi
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 42 Issue 10 Pg. 2174-6 (Oct 1994) ISSN: 0009-2363 [Print] Japan
• PMID: 7805139 (Publication Type: Journal Article)

Chemical References

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

Topics

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