Studies on Cardiac Ingredients of Plants. XIII : Chemical Modification of Gitoxin to Cardiotonic Compounds without Vascular Contractile Effect

抄録

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.