title: Anti-leishmanial activity of the bisnaphthalimidopropyl derivatives.
abstract: Bisnaphthalimidopropyl (BNIP) derivatives were recently identified as inhibitors of the Leishmania Silent Information Regulator 2 (SIR2) NAD(+)-dependent deacetylase. In this report we have for the first time, determined the potential of these compounds to treat visceral leishmaniasis using BALB/c mice chronically infected with Leishmania infantum as a model. These experiments led to the identification of BNIPdiaminooctane (BNIPDaoct) as an effective compound able to induce significant reduction of the parasite load in the spleen and in the liver. Indeed, at a dose of 1mg/kg, BNIPDaoct was more effective to treat leishmaniasis in a short course treatment (3 or 6 drug administrations) than the standard amphotericin B. Moreover, no indications of hematological toxicity were detected as evaluated by the hemoglobin, hematocrit, white and red blood cell counts, hence making BNIPDaoct a potential therapeutic agent against leishmaniasis.
authors.affiliation: IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Tavares
authors.forename: Ali
authors.initials: A
authors.lastname: Ouaissi
authors.forename: Ana Marta
authors.initials: AM
authors.lastname: Silva
authors.forename: Paul Kong Thoo
authors.initials: PK
authors.lastname: Lin
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Roy
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D053644:Naphthalimides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D059208:Parasite Load; D013154:Spleen / Q000469:parasitology
chemical_list: D000981:Antiprotozoal Agents; D053644:Naphthalimides; D000666:Amphotericin B