Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives

J Med Chem. 2005 May 19;48(10):3654-8. doi: 10.1021/jm058208o.

Abstract

Phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, beta-hematin formation, and murine Plasmodium berghei malaria. The most active antimalarial compound was 1-[3'-N-(N'-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an IC(50) of 1.76 microM for inhibition of P. falciparum development. Results suggest that chalcones exert their antimalarial activity via multiple mechanisms.

Publication types

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

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Chalcones / chemical synthesis*
  • Chalcones / chemistry
  • Chalcones / pharmacology
  • Cysteine Endopeptidases / chemistry
  • Globins / metabolism
  • Heme / chemistry
  • Hemeproteins / chemical synthesis
  • Hydrolysis
  • Malaria / drug therapy
  • Mice
  • Phenylurea Compounds / chemical synthesis*
  • Phenylurea Compounds / chemistry
  • Phenylurea Compounds / pharmacology
  • Plasmodium berghei
  • Plasmodium falciparum / drug effects
  • Polymers
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Chalcones
  • Hemeproteins
  • Phenylurea Compounds
  • Polymers
  • Protease Inhibitors
  • hemozoin
  • Heme
  • Globins
  • Cysteine Endopeptidases
  • falcipain 2