Sitamaquine overcomes ABC-mediated resistance to miltefosine and antimony in Leishmania.

ABSTRACT: Although oral miltefosine represented an important therapeutic advance in the treatment of leishmaniasis, the appearance of resistance remains a serious threat. LMDR1/LABCB4, a P-glycoprotein-like transporter included in the Leishmania ABC (ATP-binding cassette) family, was the first molecule shown to be involved in experimental miltefosine resistance. LMDR1 pumps drugs out of the parasite, thereby decreasing their intracellular accumulation. Sitamaquine, another promising oral drug for leishmaniasis, is currently in phase 2b clinical trials. The physicochemical features of this drug suggested to us that it could be considered for use as an LMDR1 inhibitor. Indeed, we report herein that nonleishmanicidal concentrations of sitamaquine reverse miltefosine resistance in a multidrug resistance

SUBMITTER: Perez-Victoria JM 

PROVIDER: S-EPMC3147638 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature