title: In vitro efficacy of 2,N-bisarylated 2-ethoxyacetamides against Plasmodium falciparum.
abstract: Investigation of a series of 2,N-bisarylated 2-ethoxyacetamides resulted in the identification of four inhibitors 5, 20, 24, 29 with single-digit micromolar in vitro efficacy against two drug-resistant Plasmodium falciparum strains. These compounds are analogs of structurally-related 1,3-bisaryl-2-propen-1-ones (chalcones), the latter showing efficacy in vitro but not in a malaria-infected mouse. The 2,N-bisarylated 2-ethoxyacetamides (e.g., 2, 5, 20) were shown to possess significantly greater stability in the presence of metabolizing enzymes than the corresponding 1,3-bisaryl-2-propen-1-ones (e.g., 1, 3, 18).
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA. Electronic address: gutterid@usna.edu.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Gutteridge
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Major
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nin
authors.affiliation: Department of Chemistry, United States Naval Academy, Annapolis, MD 21402, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Curtis
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Apurba K
authors.initials: AK
authors.lastname: Bhattacharjee
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gerena
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nichols
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002599:Chalcone / Q000737:chemistry; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D006207:Half-Life; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000962:Antimalarials; D002599:Chalcone; D002738:Chloroquine
keywords: 1,3-Diphenyl-2-propen-1-ones; 2-Ethoxyacetamide; Chalcone; Malaria; Plasmodium falciparum