A novel bufadienolide, marinosin, in the skin of the giant toad, Bufo marinus.
We have identified a novel cardiac steroid, 11,19-epoxy-19-methoxytelocinobufagin, named marinosin (1), in the skin of the toad, Bufo marinus (L.) Schneider. The treatment of compound 1 with 50% CH3CN containing 0.1% trifluoroacetic acid yielded a 11 alpha-hydroxyhellebrigenin (2), which has not previously been isolated from animals or plants. The structures of both compounds were established from spectral data obtained by NMR and MS, which were compared with those of a reference bufadienolide, 11 alpha-hydroxytelocinobufagin. Compounds 1 and 2 have A/B cis and C/D cis configuration, which is characteristic of bufadienolides such as bufalin and marinobufagin. However, the stereo-structure of compound 1 was characterized by a boat form of the B ring, which is different from the chair form in typical bufadienolides such as compound 2. Compounds 1 and 2 both exhibited activity, as demonstrated by inhibition of Na+, K(+)-ATPase enzymatic activity and by inhibition of the binding of [3H]ouabain to Na+, K(+)-ATPase; however, marinosin (1) was as less effective inhibitor than 2, 11 alpha-hydroxyhellebrigenin. We have identified compound 2 in toad venom, but not in the skin.
Matsukawa
M
M
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Akizawa
T
T
Ohigashi
M
M
Morris
J F
JF
Butler
V P
VP
Yoshioka
M
M
D000818:Animals; D002018:Bufanolides / Q000737:chemistry* / Q000494:pharmacology; D002024:Bufo marinus; D002851:Chromatography, High Pressure Liquid; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010042:Ouabain / Q000378:metabolism; D012867:Skin / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D002018:Bufanolides; C105225:marinosin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase