Effects of camptothecin, a topoisomerase I inhibitor, on Plasmodium falciparum.
Currently, the treatment of falciparum malaria is seriously compromised by spreading drug resistance. We studied the effects of camptothecin, a potent and specific topoisomerase I inhibitor, on erythrocytic malaria parasites in vitro. In Plasmodium falciparum, camptothecin trapped protein-DNA complexes, inhibited nucleic acid biosynthesis, and was cytotoxic. These results provide proof for the concept that topoisomerase I is a vulnerable target for new antimalarial drug development.
Bodley
A L
AL
Department of Medicine, The Johns Hopkins University, Baltimore, MD 21205-2185, USA.
Cumming
J N
JN
Shapiro
T A
TA
D000818:Animals; D002166:Camptothecin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D059004:Topoisomerase I Inhibitors
D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D002166:Camptothecin