title: 1,4-naphthoquinone cations as antiplasmodial agents: hydroxy-, acyloxy-, and alkoxy-substituted analogues.
abstract: Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC50 values of 17.4-49.5 nM against heteroresistant P. falciparum W2.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Ali
authors.initials: A
authors.lastname: Altharawi
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California, San Francisco , Box 0811, San Francisco, California 94143, United States.
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California, San Francisco , Box 0811, San Francisco, California 94143, United States.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia , Athens, Georgia 30602, United States ; Center for Drug Discovery, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Long
keywords: 1,4-naphthoquinones; Plasmodium; malaria; phosphonium cations