Comparison of efficacies of cysteine protease inhibitors against five strains of Plasmodium falciparum.
Falcipain-2, a cysteine protease and essential hemoglobinase of Plasmodium falciparum, is a potential antimalarial drug target. We compared the falcipain-2 sequences and sensitivities to cysteine protease inhibitors of five parasite strains that differ markedly in sensitivity to established antimalarial drugs. The sequence of falcipain-2 was highly conserved, and the sensitivities of all of the strains to falcipain-2 inhibitors were very similar. Thus, cross-resistance between cysteine protease inhibitors and other antimalarial agents is not expected in parasites that are now circulating and falcipain-2 remains a promising chemotherapeutic target.
Singh
A
A
Department of Medicine, San Francisco General Hospital and University of California, San Francisco, California 94143-0811, USA.
Rosenthal
P J
PJ
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics
D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D016054:DNA, Protozoan; D003546:Cysteine Endopeptidases; C416224:falcipain 2