title: Activity of a hydroxybibenzyl bryophyte constituent against Leishmania spp. and Trypanosoma cruzi: in silico, in vitro and in vivo activity studies.
abstract: The synthesis and potent antiprotozoal activity of 14-hydroxylunularin, a natural hydroxybibenzyl bryophyte constituent is reported. 14-hydroxylunularin was highly active in vitro assays against culture and intracellular forms of Leishmania spp. and Trypanosoma. cruzi, in absence of cytotoxicity against mammalian cells. Preliminary structure-activity relationship studies showed that the reported bioactivity depends on hybridization at the carbon-carbon bridge, position and number of free hydroxy group on the aromatic rings. The reported results were also in agreement with the in silico prediction using Non-Stochastic Quadratic Fingerprints-based algorithms. The same compound also showed antiprotozoal activity in Leishmania spp. infected mice by oral and subcutaneous administration routes, with an optimal treatment of a daily subcutaneous administration of 10 mg/kg of body weight for 15 days. This study suggested that 14-hydroxylunularin may be chosen as a new candidate in the development of leishmanicidal therapy.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Av.Gral. Flores 2124, CC 1157, Montevideo 11800, Uruguay.
authors.forename: Virginia
authors.initials: V
authors.lastname: Roldos
authors.forename: Hector
authors.initials: H
authors.lastname: Nakayama
authors.forename: Miriam
authors.initials: M
authors.lastname: Rolón
authors.forename: Alina
authors.initials: A
authors.lastname: Montero-Torres
authors.forename: Fernando
authors.initials: F
authors.lastname: Trucco
authors.forename: Susana
authors.initials: S
authors.lastname: Torres
authors.forename: Celeste
authors.initials: C
authors.lastname: Vega
authors.forename: Yovanni
authors.initials: Y
authors.lastname: Marrero-Ponce
authors.forename: Viviana
authors.initials: V
authors.lastname: Heguaburu
authors.forename: Gloria
authors.initials: G
authors.lastname: Yaluff
authors.forename: Alicia
authors.initials: A
authors.lastname: Gómez-Barrio
authors.forename: Luis
authors.initials: L
authors.lastname: Sanabria
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Ferreira
authors.forename: Antonieta
authors.initials: A
authors.lastname: Rojas de Arias
authors.forename: Enrique
authors.initials: E
authors.lastname: Pandolfi
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D001632:Bibenzyls / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D002460:Cell Line; D019295:Computational Biology; D005110:Extracellular Space / Q000187:drug effects; D005260:Female; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects; D007891:Leishmania / Q000166:cytology / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008297:Male; D051379:Mice; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: C533393:14-hydroxylunularin; D000981:Antiprotozoal Agents; D001632:Bibenzyls; D010636:Phenols