Sitamaquine

Sitamaquine (WR 6026) is an orally active Antileishmanial agent and Succinate dehydrogenase inhibitor. Sitamaquine accumulates in the acidocalcisomes of Leishmania, induces organelle alkalization, and crosses the plasma membrane of Leishmania via temperature- and energy-independent diffusion. Sitamaquine disrupts oxidative phosphorylation in Leishmania, induces mitochondrial depolarization, oxidative stress, elevated intracellular calcium, plasma membrane depolarization, and Apoptosis-like cell death. Sitamaquine can be used in the research of leishmaniasis^[1][2]. In Vitro:Sitamaquine (1-30 μM; 15 min) displaces the acidotropic probe Lysotracker Green from acidic organelles of Leishmania donovani L82, Leishmania donovani DD8, Leishmania tropica LCR-L39, and Leishmania tropica SAF-K27 promastigotes, confirming it accumulates in these organelles^[1].
Sitamaquine (5-200 μM; 0-20 min) causes a fast, irreversible reduction in intracellular ATP levels in Leishmania donovani 3-Luc promastigotes, with a 50% reduction observed at concentrations above 30 μM 10 minutes post-treatment^[2].
Sitamaquine (50-100 μM; 15 min) induces mitochondrial membrane depolarization in Leishmania donovani promastigotes, causing a 3.1-fold decrease in Rhodamine 123 accumulation with 100 μM treatment for 15 minutes, and a 3.4-fold decrease in 47% of parasites with 50 μM treatment for 15 minutes^[2].
Sitamaquine (10-200 μM; 1 h) inhibits succinate dehydrogenase activity in a mitochondrion-enriched fraction from Leishmania donovani promastigotes in a dose-dependent manner^[2].
Sitamaquine (50-100 μM; 1 h) induces phosphatidylserine externalization, a marker of apoptosis-like death, in Leishmania donovani promastigotes at 100 μM for 1 hour, causing a 1.9-fold increase in apoptotic cells relative to controls^[2].
Sitamaquine (50-100 μM; 24 h) increases the sub-G₁ DNA population, a marker of chromatin fragmentation, in Leishmania donovani promastigotes^[2].