Antiplasmodial activity of artecyclopentyl mether a new artemisinin derivative and its effect on pathogenesis in Plasmodium yoelii nigeriensis infected mice

Parasitol Res. 2011 Oct;109(4):1003-8. doi: 10.1007/s00436-011-2344-1. Epub 2011 May 4.

Abstract

In an effort to evaluate novel derivatives from artemisinin, possessing potential antimalarial activity, a new derivative artecyclopentyl mether (CPM-1) was derivatized and evaluated for its dose-dependent efficacy in Plasmodium yoelii nigeriensis infected mice. The survivability of mice at 7.5 mg/kg was >28 days with negligible parasitaemia and recovered anemia (66.16-72.62%). Artecyclopentyl mether was also found to modulate the pro- and anti-inflammatory cytokines (IFN-γ, 39.64-56.92%; TNF, 49.10-74.31%; IL-4, 11.53-43.22%; IL-10, 37.60-53.52%) favourably besides optimizing the oxidative stress to the infected subjects as evident by the nitric oxide (88.76-95.43%), lipid peroxidation (59.30-76.05%) and glycaemic data (62.70-76.66%). The results indicate the potentiality of the new derivative as an antimalarial against asexual stages of the parasite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / administration & dosage*
  • Antimalarials / chemical synthesis
  • Antimalarials / therapeutic use
  • Artemisinins / administration & dosage*
  • Artemisinins / chemical synthesis
  • Artemisinins / therapeutic use
  • Cytokines / analysis
  • Cytokines / immunology
  • Drug Resistance, Multiple
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocytes / drug effects
  • Erythrocytes / parasitology
  • Female
  • Lipid Peroxidation / drug effects
  • Malaria / drug therapy*
  • Malaria / immunology
  • Malaria / metabolism
  • Malaria / mortality
  • Malaria / pathology
  • Mice
  • Nitric Oxide / analysis
  • Nitric Oxide / biosynthesis
  • Oxidative Stress / drug effects
  • Parasitemia / drug therapy*
  • Plasmodium yoelii / drug effects*
  • Plasmodium yoelii / physiology
  • Rodent Diseases / drug therapy*
  • Rodent Diseases / immunology
  • Rodent Diseases / metabolism
  • Rodent Diseases / mortality
  • Rodent Diseases / pathology
  • Survival Rate

Substances

  • Antimalarials
  • Artemisinins
  • Cytokines
  • Nitric Oxide