Sitamaquine as a putative antileishmanial drug candidate: from the mechanism of action to the risk of drug resistance

Parasite

and J. Schrével¹  S. Cojean²  P.M. Loiseau² 

[1] Muséum National d’Histoire Naturelle, Département RDDM, UMR 7245 CNRS,CP 52, 61, rue Buffon,75231 Paris Cedex 05,France;Groupe Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Université Paris-Sud 11,92290 Châtenay-Malabry,France

关键词: drug action;    aminoquinoline;    leishmaniasis;    sitamaquine;   

Others  :  808865
DOI  :  doi:10.1051/parasite/2011182115

 received in 2010-11-24, accepted in 2011-01-09,  发布年份 2011

【 摘 要 】

Sitamaquine is a 8-aminoquinoline in development for the treatment of visceral leishmaniasis by oral route, no activity being observed on the experimental cutaneous leishmaniasis experimental models. Recent data explain how sitamaquine accumulate in Leishmania parasites, however its molecular targets remain to be identified. An advantage of sitamaquine is its short elimination half-life, preventing a rapid resistance emergence. The antileishmanial action of its metabolites is not known. The selection of a sitamaquine-resistant clone of L. donovani in laboratory and the phase II clinical trials pointing out some adverse effects such as methemoglobinemia and nephrotoxicity are considered for a further development decision.

【 授权许可】

   
© PRINCEPS Editions, Paris, 2011

【 图 表 】

Fig 1.

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