Synthesis and biological evaluation of panaxatriol derivatives against myocardial ischemia/reperfusion injury in the rat.

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]