In vitro and in vivo efficacy and in vitro metabolism of 1-phenyl-3-aryl-2-propen-1-ones against Plasmodium falciparum.
Investigation of a series of 1-phenyl-3-aryl-2-propen-1-ones resulted in the identification of nine inhibitors with submicromolar efficacy against at least one Plasmodium falciparum strain in vitro. These inhibitors were inactive when given orally in a Plasmodium berghei infected mouse model. Significant compound degradation occurred upon their exposure to a liver microsome preparation, suggesting metabolic instability may be responsible for the lack of activity in vivo.
Gutteridge
Clare E
CE
Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA. gutterid@usna.edu
Nichols
Daniel A
DA
Curtis
Sean M
SM
Thota
Darshan S
DS
Vo
Joseph V
JV
Gerena
Lucia
L
Montip
Gettayacamin
G
Asher
Constance O
CO
Diaz
Damaris S
DS
Ditusa
Charles A
CA
Smith
Kirsten S
KS
Bhattacharjee
Apurba K
AK
D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007659:Ketones / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D008862:Microsomes, Liver / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects*
D000962:Antimalarials; D007659:Ketones