title: In vitro and in vivo trypanocidal evaluation of nickel complexes with an azapurine derivative against Trypanosoma cruzi.
abstract: Seven ternary nickel(II) complexes (three previously described and four firstly described here) with an azapurine derivative (the anionic form of 4,6-dimethyl-1,2,3-triazolo[4,5-d]pyrimidin-5,7-dione) have been synthesized and spectroscopically characterized, and the crystal structures of three of them have been solved by X-ray diffraction. Studies in vitro and in vivo on the antiproliferative activity of these complexes against Trypanosoma cruzi (epimastigote, amastigote, and trypomastigote forms) have been carried out, displaying in some cases significantly higher antitrypanosomatid activity and lower toxicity than the reference drug for Chagas' disease, benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide). Ultrastructural analysis and metabolism excretion studies were also executed in order to propose a possible mechanism of action for the assayed drugs.
authors.affiliation: Department of Inorganic Chemistry, University of Granada, 18071 Granada, Spain.
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: Oscar
authors.initials: O
authors.lastname: Huertas
authors.forename: Miguel
authors.initials: M
authors.lastname: Quirós
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
authors.forename: María J
authors.initials: MJ
authors.lastname: Rosales
authors.forename: Juan M
authors.initials: JM
authors.lastname: Salas
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009532:Nickel; D021261:Parasitic Sensitivity Tests; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D014709:Vero Cells
chemical_list: D000913:Antibodies, Protozoan; D056831:Coordination Complexes; D011687:Purines; D014344:Trypanocidal Agents; D009532:Nickel