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

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.

• Authors: Andrew V Stachulski, Neil G Berry, A C Lilian Low, Shelley L Moores, Eleanor Row, David C Warhurst, Ipemida S Adagu, Jean-François Rossignol
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 4 Pg. 1450-4 (Feb 23 2006) ISSN: 0022-2623 [Print] United States
• PMID: 16480281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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