Proteome analysis of new antimalarial endoperoxide against Plasmodium falciparum.
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.
Aly
Nagwa S M
NS
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
Hiramoto
Akiko
A
Sanai
Hitomi
H
Hiraoka
Osamu
O
Hiramoto
Kazuyuki
K
Kataoka
Hiroyuki
H
Wu
Jin-Ming
JM
Masuyama
Araki
A
Nojima
Masatomo
M
Kawai
Satoru
S
Kim
Hye-Sook
HS
Wataya
Yusuke
Y
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*
D000962:Antimalarials; D010545:Peroxides; D020543:Proteome; D015800:Protozoan Proteins