![]() The first-line treatment for uncomplicated Plasmodium falciparum malaria recommended by the World Health Organization (WHO) is artemisinin (ART) combination therapies (ACTs) ( 1). We further demonstrate that in combination with ART, GNF179 effectively prevents recrudescence of dormant rings, including those bearing pfk13 propeller mutations. However, with 12 h of exposure, the compound effectively kills rings and dormant rings of both susceptible and ART-resistant parasites within 72 h. We show that GNF179 is more rapidly cidal against schizonts than against ring and trophozoite stages. Unlike DHA, GNF179 does not induce dormancy. Here, we characterized the stage of action of the IPZ GNF179 and evaluated its activity against rings and dormant rings in wild-type and ART-resistant parasites. The imidazolopiperazines (IPZ) are a novel class of antimalarial drugs that have demonstrated efficacy in early clinical trials. These quiescent rings are referred to as dormant rings or DHA-pretreated rings (here called dormant rings). Early rings can enter a state of quiescence upon DHA exposure and resume growth in its absence. ![]() Phenotypically, ART resistance is defined as delayed parasite clearance in patients due to the reduced susceptibility of early ring-stage parasites to the active metabolite of ART dihydroartemisinin (DHA). ![]() ART resistance has been associated with mutations in the Plasmodium falciparum kelch-13 ( Pfk13) propeller domain. Artemisinin (ART) resistance has spread through Southeast Asia, posing a serious threat to the control and elimination of malaria.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |