Identification of isoflavone derivatives as effective anticryptosporidial agents in vitro and in vivo

J Med Chem. 2006 Feb 23;49(4):1450-4. doi: 10.1021/jm050973f.

Abstract

We report the preparation and antiparasitic activity in vitro and in vivo of a series of isoflavone derivatives related to genistein. These analogues retain the 5,7-dihydroxyisoflavone core of genistein: direct genistein analogues (2-H isoflavones), 2-carboethoxy isoflavones, and the precursor deoxybenzoins were all evaluated. Excellent in vitro activity against Cryptosporidium parvum was observed for both classes of isoflavones in cell cultures, and the lead compound 19, RM6427, shows high in vivo efficacy against an experimental infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Line, Tumor
  • Coccidiostats / chemical synthesis*
  • Coccidiostats / pharmacology
  • Cryptosporidiosis / drug therapy
  • Cryptosporidium parvum / drug effects*
  • Cryptosporidium parvum / isolation & purification
  • Female
  • Genistein / analogs & derivatives
  • Genistein / chemical synthesis
  • Genistein / pharmacology
  • Gerbillinae
  • Humans
  • Immunocompromised Host
  • Isoflavones / chemical synthesis*
  • Isoflavones / pharmacology
  • Male
  • Structure-Activity Relationship

Substances

  • 3-(3-bromophenyl)-5,7-dihydroxy-4-oxo-4H-chromene-2-carboxylic acid ethyl ester
  • Coccidiostats
  • Isoflavones
  • Genistein