Cardiac glycosides from Antiaris toxicaria with potent cardiotonic activity.
An ethanolic extract of Antiaris toxicaria trunk bark showed potent in vitro cardiotonic effect on isolated guinea pig atria. Bioassay-guided fractionation of the extract led to identification of nine new cardiac glycosides (1-9, named antiarosides A-I), antiarotoxinin A (10), and 18 known compounds. Their structures were established using MS and NMR spectroscopic studies, including homonuclear and heteronuclear correlation experiments. The ability of these cardiotonic compounds to produce positive inotropic action and their safety indexes were examined in comparison with those of ouabain, a classical inhibitor of Na(+)/K(+)-ATPase. Malayoside (23) was nearly equipotent and had a similar safety index to ouabain in guinea pig atria. However, the maximal positive inotropic effect and safety index of 23 in papillary muscle were better than those of ouabain. An electrophysiological recording showed that 23 inhibited the sodium pump current in a concentration-dependent manner.
Shi
Li-Shian
LS
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Liao
Yu-Ren
YR
Su
Ming-Jai
MJ
Lee
An-Sheng
AS
Kuo
Ping-Chung
PC
Damu
Amooru G
AG
Kuo
Sheng-Chu
SC
Sun
Han-Dong
HD
Lee
Kuo-Hsiung
KH
Wu
Tian-Shung
TS
D000818:Animals; D031621:Antiaris / Q000737:chemistry*; D002301:Cardiac Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase