Search

Panaxatriol, a triterpene bearing a steroid-like structure similar to cardiac glycosides, was presumed to share the same bioactivity with cardiac glycosides, and may be a potential Na + , K + -ATPase inhibitor. In this paper, a series of panaxatriol derivatives were synthesized and evaluated for Na + , K + -ATPase inhibitory activities. The results of biological tests showed that more than half of the synthesized derivatives presented increased inhibitory activities compared with panaxatriol. Of these compounds, 13a with a 3, 4- seco skeleton showed the most potent inhibitory activity, which was equal to that of the standard drug digoxin. To understand the binding mode of the most active compound, molecular docking study of 13a with Na + , K + -ATPase was conducted. Therefore, 13a may serve as a new lead compound for the development of novel Na + , K + -ATPase inhibitors. [ABSTRACT FROM AUTHOR]

Panaxatriol (PT) is a natural product derived from ginseng that possesses cardioprotective effects in isolated rat hearts. To develop more potent therapeutic agents against myocardial ischemia/reperfusion (MI/R) injury from natural products, a novel series of heterocycle ring-fused panaxatriol derivatives were designed and synthesized. In vitro results showed that approximately half of them exhibited increased cytoprotective activity compared with PT in a cardiomyocyte model of oxygen-glucose deprivation and reperfusion (OGD/R) injury. Furthermore, the in vitro activity of the representative derivative, compound 18 , was also confirmed in a rat model of MI/R injury. In vivo results showed that 18 can markedly reduce myocardial infarction size, decrease circulating cardiac troponin I (cTnI) leakage, and alleviate cardiac tissue damage in the rats. Therefore, these findings provide the basis for further development of novel anti-MI/R injury agents. Image 1 • A series of heterocycle ring-fused panaxatriol (PT) derivatives were designed and synthesized. • The compounds were evaluated for cardioprotective activity in a cardiomyocyte model of OGD/R injury. • Approximately half of the PT derivatives exhibited more potent cytoprotective activity than PT. • Representative compound, 18 , attenuated the reperfusion injury in a rat model of myocardial infarction. [ABSTRACT FROM AUTHOR]