Antimalarial Eudesmane Sesquiterpenoids from Dobinea delavayi

J Nat Prod. 2020 Apr 24;83(4):927-936. doi: 10.1021/acs.jnatprod.9b00761. Epub 2020 Apr 1.

Abstract

Eleven new angeloylated eudesmane sesquiterpenoids, dobinins D-N (2, 3, 5, 6, 8, 9, and 11-15), and four known compounds (1, 4, 7, and 10) were isolated from the roots of Dobinea delavayi. A new oxidation product (8a) was also obtained from dobinin H (8). Their structures were elucidated by spectroscopic data and single-crystal X-ray diffraction analyses. Dobinins K-N (12-15) are the first examples of rearrangement noreudesmane analogue sesquiterpenoids with a unique 6/5-fused carbon skeleton. A putative biosynthetic pathway of compounds 12-15 is proposed. Compound 12 exhibited significant antimalarial activity superior to artemisinin with the inhibition ratio of 59.1%, and compounds 3, 5, and 15 exhibited moderate antimalarial activities against Plasmodium yoelii BY265RFP with inhibition ratios ranging from 14.5% to 18.5% at a dose of 30 mg/kg/day. In addition, the apoptosis of P. yoelii BY265RFP by the depolarization of mitochondrial membrane potential with striking ROS production, after parasitized erythrocyte lysis mediated by cytokines IL-12 and IFN-γ, may be a possible mechanism of antimalarial action of compound 12 against P. yoelii BY265RFP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anacardiaceae / chemistry*
  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Apoptosis / drug effects
  • Cytokines / physiology
  • Erythrocytes / parasitology
  • Malaria / drug therapy
  • Malaria / parasitology
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Roots / chemistry
  • Plasmodium yoelii / drug effects
  • Reactive Oxygen Species / metabolism
  • Sesquiterpenes, Eudesmane / chemistry*
  • Sesquiterpenes, Eudesmane / pharmacology*
  • X-Ray Diffraction

Substances

  • Antimalarials
  • Cytokines
  • Plant Extracts
  • Reactive Oxygen Species
  • Sesquiterpenes, Eudesmane