Effect of the aggregated protein dye YAT2150 on parasite viability.

The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC) of approximately 0.5 µM against promastigote and amastigote stages of . The encapsulation in liposomes of YAT2150 significantly improved its IC to 0.37 and 0.19 µM in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 µM. YAT2150 became strongly fluorescent when binding intracellular protein deposits in cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite , the inhibition of protein aggregation. In , YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both and , thus being a potential drug for the treatment of co-infections of both parasites.