title: Proteome analysis of new antimalarial endoperoxide against Plasmodium falciparum.
abstract: N-89, a new antimalarial endoperoxide, was selected as a promising antimalarial compound showing high activity and selectivity. To study the mechanism of N-89 action, N-89 resistant strain (NRC10) was obtained by intermittent drug pressure. NRC10 had a tenfold increase in the EC(50) value of N-89. No cross-resistance was obtained with other antimalarial compounds. Comparative proteome analysis of N-89 sensitive and NRC10 strains revealed over-expression of 12 spots and down-regulation of 14 spots in NRC10. Fifteen proteins were identified of Plasmodium falciparum origin. The identified proteins representing several functions, mainly related to the glycolytic pathway, and metabolism of protein and lipid. Our results suggest that identified proteins may be candidates of antimalarial endoperoxide targets.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
authors.forename: Nagwa S M
authors.initials: NS
authors.lastname: Aly
authors.forename: Akiko
authors.initials: A
authors.lastname: Hiramoto
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sanai
authors.forename: Osamu
authors.initials: O
authors.lastname: Hiraoka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hiramoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kataoka
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Wu
authors.forename: Araki
authors.initials: A
authors.lastname: Masuyama
authors.forename: Masatomo
authors.initials: M
authors.lastname: Nojima
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Wataya
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D021261:Parasitic Sensitivity Tests; D010545:Peroxides / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000187:drug effects*; D020543:Proteome / Q000187:drug effects*; D015800:Protozoan Proteins / Q000032:analysis*
chemical_list: D000962:Antimalarials; D010545:Peroxides; D020543:Proteome; D015800:Protozoan Proteins