Bouzón-Arnáiz Inés, Rawat Mukul, Coyle Rachael, Feufack-Donfack Lionel Brice, Ea Malen, Orban Agnes, Popovici Jean, Román-Álamo Lucía, Fallica Antonino Nicolò, Domínguez-Asenjo Bárbara, Moreno Javier, Arce Elsa M, Mallo-Abreu Ana, Muñoz-Torrero Diego, Lee Marcus C S, Fernàndez-Busquets Xavier
Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-University of Barcelona), Rosselló 149-153, Barcelona, 08036, Spain.
Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, Barcelona, 08028, Spain.
Sci Rep. 2025 Jan 23;15(1):2941. doi: 10.1038/s41598-025-85346-y.
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 Plasmodium falciparum parasites resistant to YAT2150 concentrations ranging from 3× to 0.25× the in vitro IC of the compound (in the two-digit nM range) and performed a cross-resistance assessment in P. falciparum 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 Plasmodium vivax (IC between 4 and 36 nM) and Leishmania infantum (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.
我们最近对聚集蛋白染料YAT2150的强效抗疟原虫活性进行了表征，其推测的作用模式是抑制疟原虫中的蛋白质聚集。使用单剂量和递增方法，进行了试验，以选择对YAT2150浓度具有抗性的恶性疟原虫，该浓度范围为该化合物体外半数抑制浓度（IC）的3倍至0.25倍（在两位数的纳摩尔范围内），并对携带使其对多种抗疟药物产生抗性的突变的恶性疟原虫品系进行了交叉抗性评估。孵育60天后，体外未出现抗性疟原虫，这表明YAT2150是一种“不可抗拒”的抗疟药物。冻干化合物在25°C下储存至少一年是稳定的。在临床分离株中进行的测试表明，YAT2150对间日疟原虫（IC在4至36 nM之间）和婴儿利什曼原虫（1.27和1.11 µM）也具有很强的活性，使其成为一种独特的化合物，有望成为第一种用于治疗疟疾和利什曼病的药物。
