Studies on cardiac ingredients of plants. XIII: Chemical modification of gitoxin to cardiotonic compounds without vascular effect

Chem Pharm Bull (Tokyo). 1997 Apr;45(4):599-607. doi: 10.1248/cpb.45.599.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bufanolides / chemistry
  • Bufanolides / pharmacology
  • Cardiotonic Agents / chemistry*
  • Cardiotonic Agents / pharmacology
  • Digoxin / analogs & derivatives*
  • Digoxin / chemistry
  • Digoxin / pharmacology
  • Dogs
  • Guinea Pigs
  • Kidney / enzymology
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Plants, Medicinal / chemistry*
  • Rats
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Stimulation, Chemical
  • Structure-Activity Relationship

Substances

  • Bufanolides
  • Cardiotonic Agents
  • Digoxin
  • Sodium-Potassium-Exchanging ATPase
  • bufotoxin
  • gitoxin