title: In vitro evaluation of new terpenoid derivatives against Leishmania infantum and Leishmania braziliensis.
abstract: The activity of five (1-5) abietane phenol derivatives against Leishmania infantum and Leishmania braziliensis was studied using promastigotes and axenic and intracellular amastigotes. Infectivity and cytotoxicity tests were performed with J774.2 macrophage cells using Glucantime as a reference drug. The mechanisms of action were analysed by performing metabolite excretion and transmission electron microscopy ultrastructural studies. Compounds 1-5 were more active and less toxic than Glucantime. The infection rates and mean number of parasites per cell observed in amastigote experiments showed that derivatives 2, 4 and 5 were the most effective against both L. infantum and L. braziliensis. The ultrastructural changes observed in the treated promastigote forms confirmed that the greatest cell damage was caused by the most active compound (4). Only compound 5 caused changes in the nature and amounts of catabolites excreted by the parasites, as measured by ¹H nuclear magnetic resonance spectroscopy. All of the assayed compounds were active against the two Leishmania species in vitro and were less toxic in mammalian cells than the reference drug.
authors.affiliation: Department of Parasitology, University of Granada, Granada, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ramírez-Macías
authors.forename: Clotilde
authors.initials: C
authors.lastname: Marín
authors.forename: Rachid
authors.initials: R
authors.lastname: Chahboun
authors.forename: Francisco
authors.initials: F
authors.lastname: Olmo
authors.forename: Ibtisam
authors.initials: I
authors.lastname: Messouri
authors.forename: Oscar
authors.initials: O
authors.lastname: Huertas
authors.forename: María Jose
authors.initials: MJ
authors.lastname: Rosales
authors.forename: Ramón
authors.initials: R
authors.lastname: Gutierrez-Sánchez
authors.forename: Enrique
authors.initials: E
authors.lastname: Alvarez-Manzaneda
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D020128:Inhibitory Concentration 50; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000648:ultrastructure; D018314:Leishmania infantum / Q000187:drug effects* / Q000648:ultrastructure; D008264:Macrophages / Q000469:parasitology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D021261:Parasitic Sensitivity Tests; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D013729:Terpenes