Synthesis and antimalarial activity of quinones and structurally-related oxirane derivatives

Eur J Med Chem. 2016 Jan 27:108:134-140. doi: 10.1016/j.ejmech.2015.11.020. Epub 2015 Nov 27.

Abstract

A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 μM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule.

Keywords: Epoxides; Infectious disease; Lapachone; Malaria; Naphthoquinones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Ethylene Oxide / chemical synthesis
  • Ethylene Oxide / chemistry*
  • Ethylene Oxide / pharmacology*
  • Fibroblasts / drug effects
  • Humans
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Quinones / chemical synthesis*
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Quinones
  • Ethylene Oxide