Identification of isoflavone derivatives as effective anticryptosporidial agents in vitro and in vivo.
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.
Romark Centre for Drug Discovery, Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK. stachuls@liv.ac.uk
Andrew V
AV
Stachulski
Neil G
NG
Berry
A C
AC
Lilian Low
Shelley L
SL
Moores
Eleanor
E
Row
David C
DC
Warhurst
Ipemida S
IS
Adagu
Jean-François
JF
Rossignol
D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D003049:Coccidiostats / Q000138:chemical synthesis* / Q000494:pharmacology; D003457:Cryptosporidiosis / Q000188:drug therapy; D016785:Cryptosporidium parvum / Q000187:drug effects* / Q000302:isolation & purification; D005260:Female; D019833:Genistein / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D005849:Gerbillinae; D006801:Humans; D016867:Immunocompromised Host; D007529:Isoflavones / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D013329:Structure-Activity Relationship
C509274:3-(3-bromophenyl)-5,7-dihydroxy-4-oxo-4H-chromene-2-carboxylic acid ethyl ester; D003049:Coccidiostats; D007529:Isoflavones; D019833:Genistein