title: (-)-α-Bisabolol, a Promising Oral Compound for the Treatment of Visceral Leishmaniasis.
abstract: The aim of the present study was to assess the in vitro and in vivo activity of (-)-α-bisabolol (1) against the etiological agents of visceral leishmaniasis. Bone-marrow-derived macrophages were infected with Leishmania infantum or L. donovani promastigotes and incubated with (-)-α-bisabolol at different concentrations. Pentamidine isethionate and meglumine antimoniate were used as reference drugs. Inhibitory concentration 50% (IC50) and cytotoxic concentration 50% (CC50) were calculated. Balb/c mice were infected intraperitoneally with stationary-phase promastigotes. They were treated with (-)-α-bisabolol at different doses orally, meglumine antimoniate at 104 mg Sb(V)/kg, or a combination of both. (-)-α-Bisabolol proved to be innocuous to mammal cells and active against L. infantum and L. donovani intracellular amastigotes (IC50 55 and 39 μM, respectively). Compound 1 also proved to be active in an in vivo model of visceral leishmaniasis due to L. infantum, as it reduced parasite load in the spleen and liver by 71.60% and 89.22%, respectively, at 200 mg/kg without showing toxicity. (-)-α-Bisabolol (1) is a nontoxic compound that was proven to be active against visceral leishmaniasis in an in vivo murine model orally. It was more effective than meglumine antimoniate at reducing spleen parasite load and as effective as this antimonial drug in the liver.
authors.affiliation: †Departamento de Parasitología and ‡Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Corpas-López
authors.affiliation: †Departamento de Parasitología and ‡Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Morillas-Márquez
authors.affiliation: †Departamento de Parasitología and ‡Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: M Concepción
authors.initials: MC
authors.lastname: Navarro-Moll
authors.affiliation: †Departamento de Parasitología and ‡Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Merino-Espinosa
authors.affiliation: †Departamento de Parasitología and ‡Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Díaz-Sáez
authors.affiliation: †Departamento de Parasitología and ‡Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: Joaquina
authors.initials: J
authors.lastname: Martín-Sánchez
mesh_terms: D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000627:therapeutic use*; D013237:Stereoisomerism
chemical_list: D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; C004497:bisabolol