Antisense oligodeoxynucleotides: useful tool for search and assessment of new targets for anti-malarial drugs.
We investigated about targeting for new antimalarial drugs using antisense (AS) oligodeoxynucleotides (ODNs). Synthetic nuclease-resistant ODNs (phosphorothioate (PS) ODNs and ODNs containing 4'alpha-C-(2-aminoethyl)thymidines (4'-amino ODNs)) which target mitochondrial succinate dehydrogenase (SDH) iron-sulfur subunit (IP), had antimalarial activity (EC50; about 1.0 microM). Furthermore we showed that intra-parasitic SDH IP mRNA levels, which were detected using quantitative RT-PCR assay, were decreased 13% of control after the 24 h expose to SDH IP AS. From the results, we conclude that SDH has potential as the target for novel antimalarials, and AS ODNs is effective for search and assessment of targets for new antimalarial drugs.
Ikemoto
N
N
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Japan.
Kim
H S
HS
Kanazaki
M
M
Ueno
Y
Y
Shuto
S
S
Matsuda
A
A
Wataya
Y
Y
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D015195:Drug Design; D007506:Iron-Sulfur Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics; D013873:Thionucleotides; D014158:Transcription, Genetic / Q000187:drug effects
D000962:Antimalarials; D007506:Iron-Sulfur Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D013873:Thionucleotides; D013385:Succinate Dehydrogenase