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Title

Uptake of the antileishmania drug tafenoquine follows a sterol-dependent diffusion process in Leishmania.

AuthorsManzano, José Ignacio; Carvalho, L.; García-Hernández, Raquel; Poveda, J. A.; Ferragut, J. A.; Castanys, Santiago; Gamarro, Francisco
Issue Date2011
PublisherOxford University Press
CitationJournal of Antimicrobial Chemotherapy 66: 2562- 2565 (2011)
AbstractObjectives The present study was designed to elucidate the mechanism of tafenoquine uptake in Leishmania and its sterol dependence. Methods Because tafenoquine is a fluorescent compound, spectrofluorimetric analysis allowed us to monitor its uptake by Leishmania promastigotes and intracellular amastigotes, and to evaluate the effect of temperature, energy and H(+) gradient on drug entry. The influence of sterols on tafenoquine uptake in Leishmania parasites was determined in experiments using sterol-depleting agents such as methyl-ß-cyclodextrin or cholesterol oxidase. Results Tafenoquine exhibited fast entry kinetics into Leishmania in an energy-independent, but pH- and temperature-dependent, non-saturable process. Furthermore, sterol depletion decreased tafenoquine uptake. Conclusions These findings suggest that Leishmania takes up tafenoquine by a diffusion process and that decreases in membrane sterol content may induce a decrease in drug uptake.
URIhttp://hdl.handle.net/10261/80077
DOI10.1093/JAC/DKR345
Identifiersdoi: 10.1093/JAC/DKR345
issn: 0305-7453
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