Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of <i>Plasmodium falciparum</i>.

ABSTRACT: Malaria tropica, caused by Plasmodium falciparum (P. falciparum), remains a global health challenge with limited therapeutic options. In mammalian cells, the small-molecule compound RAS-selective lethal 3 (RSL3) induces ferroptosis via lipid peroxidation. In this study, we demonstrate that RSL3 synergizes with Pyrimethamine, an inhibitor of P. falciparum dihydrofolate reductase (DHFR), to suppress parasite proliferation in red blood cells (RBCs). A similar synergistic effect was observed with Cycloguanil, a structural analog of Pyrimethamine, but not with other DHFR inhibitors or alternative agents that induce ferroptosis in nucleated mammalian cells. Notably, Ferrostatin-1, an antagonist of lipid peroxidation, largely failed to rescue parasite growth in the presence o

SUBMITTER: Nikolova V 

PROVIDER: S-EPMC12486841 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature