title: Sitamaquine as a putative antileishmanial drug candidate: from the mechanism of action to the risk of drug resistance.
abstract: 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.
authors.affiliation: Groupe Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Université Paris-Sud 11, 92290 Châtenay-Malabry, France. philippe.loiseau@u-psud.fr
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: S
authors.initials: S
authors.lastname: Cojean
authors.forename: J
authors.initials: J
authors.lastname: Schrével
mesh_terms: D000284:Administration, Oral; D000634:Aminoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D004195:Disease Models, Animal; D004351:Drug Resistance; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*
chemical_list: D000634:Aminoquinolines; D000981:Antiprotozoal Agents; C080436:8-aminoquinoline