2. Academic Validation
  3. Design, synthesis and anti-inflammatory activity of 3-amino acid derivatives of ocotillol-type sapogenins

Design, synthesis and anti-inflammatory activity of 3-amino acid derivatives of ocotillol-type sapogenins

  • Eur J Med Chem. 2020 Sep 15;202:112507. doi: 10.1016/j.ejmech.2020.112507.
Gangqiang Yang 1,  Meng Gao 2,  Yixiao Sun 2,  Conghui Wang 2,  Xiaojuan Fang 2,  Hongyan Gao 2,  Wenshuang Diao 2,  Hui Yu 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, China. Electronic address: oceanygq@ytu.edu.cn.
  • 2 School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, China.
  • 3 College of Food Engineering, Ludong University, Yantai, 264025, China. Electronic address: zoehuihui@hotmail.com.
PMID: 32650181 DOI: 10.1016/j.ejmech.2020.112507
Abstract

Ocotillol-type sapogenins (OTS) are major ginsenoside metabolites in human hepatic tissue. In order to better utilize OTS and derivatives thereof as anti-inflammatory compounds, present study produced multiple novel 3-amino acid OTS derivatives and evaluated their anti-inflammatory activity in vitro. The nitric oxide (NO) inhibitory activity of these compounds was used for OTS structure-activity relationship (SAR) evaluations, revealing that both R/S stereochemistry at C-24 and the amino acid type at C-3 influence such NO inhibitory activity. This activity was highest for an N-Boc-protected neutral aliphatic amino acid derivative of 24R-OTS (5a), which performed better than even hydrocortisone sodium succinate in vitro. Compound 5a was also able to markedly suppress the LPS-induced upregulation of TNF-α, IL-6, iNOS, and COX-2 via the NF-κB and MAPK pathways. This suggests that OTS derivatives may be valuable anti-inflammatory compounds worthy of further preclinical evaluation.

Keywords

Anti-inflammatory activity; Ginsenosides; NF-κB and MAPK pathways; Ocotillol-type sapogenins; Structure-activity relationship.

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