Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds

Bioorg Med Chem. 2010 Dec 1;18(23):8243-56. doi: 10.1016/j.bmc.2010.10.009. Epub 2010 Oct 31.

Abstract

A targeted series of chalcone and dienone hybrid compounds containing aminoquinoline and nucleoside templates was synthesized and evaluated for in vitro antimalarial activity. The Cu(I)-catalyzed cycloaddition of azides and terminal alkynes was applied as the hybridization strategy. Several chalcone-chloroquinoline hybrid compounds were found to be notably active, with compound 8b the most active, exhibiting submicromolar IC(50) values against the D10, Dd2 and W2 strains of Plasmodium falciparum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Aminoquinolines / chemistry
  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Azides / chemistry
  • Catalysis
  • Chalcone / chemistry*
  • Chalcones / chemical synthesis*
  • Chalcones / chemistry
  • Chalcones / pharmacology
  • Copper / chemistry
  • Drug Design
  • Hemin / metabolism
  • Nucleosides / chemistry
  • Plasmodium falciparum / drug effects
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemistry*

Substances

  • 3-(4-(1-(7-chloroquinolin-4-yl)-1H-(1,2,3)triazol-4-ylmethoxy)-3-methoxyphenyl)-1-(2,4-dimethoxyphenyl)propenone
  • Alkynes
  • Aminoquinolines
  • Antimalarials
  • Azides
  • Chalcones
  • Nucleosides
  • Quinolines
  • Triazoles
  • Chalcone
  • Hemin
  • Copper