YAT2150 is irresistible in <em>Plasmodium falciparum</em> and active against <em>Plasmodium vivax</em> and <em>Leishmania </em>clinical isolates

Abstract

We recently characterized the potent antiplasmodial activity of the aggregated protein dye YAT2150, whose presumed mode of action is the inhibition of protein aggregation in the malaria parasite. Using single-dose and ramping methods, assays were done to select <em>Plasmodium falciparum</em> parasites resistant to YAT2150 concentrations ranging from 3× to 0.25× the in vitro IC₅₀ of the compound (in the two-digit nM range) and performed a cross-resistance assessment in <em>P. falciparum</em> lines harboring mutations that make them resistant to a variety of antimalarial drugs. Resistant parasites did not emerge in vitro after 60 days of incubation, which postulates YAT2150 as an ‘irresistible’ antimalarial. The lyophilized compound is stable for at least one year stored at 25 °C. Tests performed in clinical isolates indicated that YAT2150 had also strong activity against <em>Plasmodium vivax</em> (IC₅₀ between 4 and 36 nM) and <em>Leishmania infantum</em> (1.27 and 1.11 µM), placing it as a unique compound with perspectives of becoming the first drug to be used against both malaria and leishmaniasis.