Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18100 Armilla, Granada, Spain.
Sitamaquine (WR6026), an 8-aminoquinoline derivative, is a new antileishmanial oral drug. As a lipophilic weak base, it rapidly accumulates in acidic compartments, mainly represented by acidocalcisomes. In this work, we show that the antileishmanial action of sitamaquine is unrelated with their level of accumulation in these acidic vesicles. We have observed significant differences in sitamaquine sensitivity and accumulation between Leishmania species and strains, and interestingly there is no correlation between them. However, there is a relationship between the levels of accumulation of sitamaquine and acidotropic probes, acidocalcisomes size and polyphosphate levels. L. major AP3delta-null mutant line, in which acidocalcisomes are devoid of their usual polyphosphate and proton content, are unable to accumulate sitamaquine; however, both parental and AP3delta-null mutants showed similar sensitivity to sitamaquine. Our findings provide clear evidence that antileishmanial action of sitamaquine is unrelated to its accumulation in acidocalcisomes.