Synthesis and bioevaluation of novel 4-aminoquinoline-tetrazole derivatives as potent antimalarial agents

Eur J Med Chem. 2013 Aug:66:69-81. doi: 10.1016/j.ejmech.2013.05.023. Epub 2013 May 28.

Abstract

A series of novel tetrazole derivatives of 4-aminoquinoline were synthesized and screened for their antimalarial activities against both chloroquine-senstive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum as well as for cytotoxicity against VERO cell lines. Most of the synthesized compounds exhibited potent antimalarial activity as compared to chloroquine against K1-strain. Compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in Swiss mice against Plasmodium yoelii following both intraperitoneal (ip) and oral administration, wherein compounds 20 and 23 each showed in vivo suppression of 99.99% parasitaemia on day 4.

Keywords: 4-Aminoquinoline; Antimalarial; Chloroquine; Cytotoxicity; Tetrazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemical synthesis*
  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Aminoquinolines / toxicity
  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antimalarials / toxicity
  • Chemistry Techniques, Synthetic
  • Chlorocebus aethiops
  • Hemeproteins / antagonists & inhibitors
  • Inhibitory Concentration 50
  • Male
  • Mice
  • Plasmodium falciparum / drug effects
  • Rats
  • Tetrazoles / chemistry*
  • Vero Cells

Substances

  • Aminoquinolines
  • Antimalarials
  • Hemeproteins
  • Tetrazoles
  • 1H-tetrazole
  • hemozoin
  • 4-aminoquinoline