title: In vitro anti-leishmania evaluation of nickel complexes with a triazolopyrimidine derivative against Leishmania infantum and Leishmania braziliensis.
abstract: Studies on the anti-proliferative activity in vitro of seven ternary nickel (II) complexes with a triazolopyrimidine derivative and different aliphatic or aromatic amines as auxiliary ligands against promastigote and amastigote forms of Leishmania infantum and Leishmania braziliensis have been carried out. These compounds are not toxic for the host cells and two of them are effective at lower concentrations than the reference drug used in the present study (Glucantime). In general, the in vitro growth rate of Leishmania spp. was reduced, its capacity to infect cells was negatively affected and the multiplication of the amastigotes decreased. Ultrastructural analysis and metabolism excretion studies were executed in order to propose a possible mechanism for the action of the assayed compounds. Our results show that the potential mechanism is at the level of organelles membranes, either by direct action on the microtubules or by their disorganization, leading to vacuolization, degradation and ultimately cell death.
authors.affiliation: Departamento de Parasitología, Universidad de Granada, 18071 Granada, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ramírez-Macías
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Maldonado
authors.forename: Clotilde
authors.initials: C
authors.lastname: Marín
authors.forename: Francisco
authors.initials: F
authors.lastname: Olmo
authors.forename: Ramón
authors.initials: R
authors.lastname: Gutiérrez-Sánchez
authors.forename: María J
authors.initials: MJ
authors.lastname: Rosales
authors.forename: Miguel
authors.initials: M
authors.lastname: Quirós
authors.forename: Juan M
authors.initials: JM
authors.lastname: Salas
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000378:metabolism; D018314:Leishmania infantum / Q000187:drug effects* / Q000378:metabolism; D008024:Ligands; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009532:Nickel / Q000737:chemistry / Q000494:pharmacology*; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure*; D021261:Parasitic Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D002413:Cations, Divalent; D056831:Coordination Complexes; D008024:Ligands; D011743:Pyrimidines; D014230:Triazoles; D009532:Nickel