title: In vitro and in vivo efficacy and in vitro metabolism of 1-phenyl-3-aryl-2-propen-1-ones against Plasmodium falciparum.
abstract: 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.
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA. gutterid@usna.edu
authors.forename: Clare E
authors.initials: CE
authors.lastname: Gutteridge
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nichols
authors.forename: Sean M
authors.initials: SM
authors.lastname: Curtis
authors.forename: Darshan S
authors.initials: DS
authors.lastname: Thota
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Vo
authors.forename: Lucia
authors.initials: L
authors.lastname: Gerena
authors.forename: Gettayacamin
authors.initials: G
authors.lastname: Montip
authors.forename: Constance O
authors.initials: CO
authors.lastname: Asher
authors.forename: Damaris S
authors.initials: DS
authors.lastname: Diaz
authors.forename: Charles A
authors.initials: CA
authors.lastname: Ditusa
authors.forename: Kirsten S
authors.initials: KS
authors.lastname: Smith
authors.forename: Apurba K
authors.initials: AK
authors.lastname: Bhattacharjee
mesh_terms: 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*
chemical_list: D000962:Antimalarials; D007659:Ketones