title: Studies on cardiac ingredients of plants. XIII: Chemical modification of gitoxin to cardiotonic compounds without vascular effect.
abstract: Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations, and the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats. Most of the compounds showed a smaller contractile effect on the arterial muscle. Among these compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological activities, such as PIE comparable to that of 1, 1.25 times wider concentration-dependent range than 1, and lack of contractile activity on vascular muscle.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nagatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Takemoto
authors.forename: K
authors.initials: K
authors.lastname: Shibatomi
authors.forename: S
authors.initials: S
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.forename: J
authors.initials: J
authors.lastname: Sakakibara
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Hotta
authors.forename: K
authors.initials: K
authors.lastname: Takeya
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Asakawa
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000737:chemistry / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000737:chemistry* / Q000494:pharmacology; D004077:Digoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D007668:Kidney / Q000201:enzymology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
chemical_list: D002018:Bufanolides; D002316:Cardiotonic Agents; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; C026738:bufotoxin; C005003:gitoxin