title: Partial synthetic derivatization of canrenone and characterization of its impact on the inhibitory effect on Na+/K(+)-ATPase activity in human heart muscle.
abstract: To improve the weak inhibitory effect of 3-oxo-17 alpha-pregna-4,6-diene-21,17-carbolactone (canrenone, II) on Na+/K(+)-ATPase activity in human heart muscle, we have investigated the impact of hydrogenation, reduction, glycosidation, and the introduction of a 3-sulfonamido residue on the inhibitory potency of canrenone. The greatest increase in potency (> 20 times) was found for 3 beta-(alpha-L-rhamnopyranosyloxy)-5 beta, 17 alpha-pregnane-21, 17-carbolactone (IX). The 3-O-glycosides IX-XI are the first representatives of C/D-trans steroids with effector-receptor complex decay half-times longer than those of therapeutically used cardenolides.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Weiland
authors.forename: R
authors.initials: R
authors.lastname: Megges
authors.forename: B
authors.initials: B
authors.lastname: Undeutsch
authors.forename: R
authors.initials: R
authors.lastname: Schön
authors.forename: H
authors.initials: H
authors.lastname: Büchting
authors.forename: R H
authors.initials: RH
authors.lastname: Repke
mesh_terms: D002192:Canrenone / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006027:Glycosides / Q000737:chemistry; D006801:Humans; D006865:Hydrogenation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009206:Myocardium / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D006027:Glycosides; D013449:Sulfonamides; D002192:Canrenone; D000254:Sodium-Potassium-Exchanging ATPase