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

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

  • Eur J Med Chem. 2020 Jan 1;185:111729. doi: 10.1016/j.ejmech.2019.111729.
Qiong Wu 1,  Ruiying Wang 2,  Yang Shi 1,  Wenchao Li 1,  Meng Li 3,  Peng Chen 1,  Bowen Pan 1,  Qing Wang 1,  Caifeng Li 4,  Jianbing Wang 5,  Guibo Sun 2,  Xiaobo Sun 2,  Hongzheng Fu 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Science, Peking University, Beijing, 100191, PR China.
  • 2 Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, PR China.
  • 3 Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United Kingdom.
  • 4 College of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
  • 5 Guangdong-Macau Traditional Chinese Medicine Technology Industrial Park Development Co., Ltd, Zhuhai, 519000, PR China.
  • 6 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Science, Peking University, Beijing, 100191, PR China. Electronic address: [email protected].
PMID: 31655431 DOI: 10.1016/j.ejmech.2019.111729
Abstract

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.

Keywords

Heterocyclic compounds; Ischemia/reperfusion injury; Panaxatriol; Structure-activity relationships; Synthesis.

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