title: Lanthanide complexes containing 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)-one and their therapeutic potential to fight leishmaniasis and Chagas disease.
abstract: In the last years, numerous and significant advances in lanthanide coordination chemistry have been achieved. The unique chemical nature of these metal ions which is conferred by their f-electrons has led to a wide range of coordination compounds with interesting structural, physical and also biological properties. Consequently, lanthanide complexes have found applications mainly in catalysis, gas adsorption, photochemistry and as diagnostic tools. However, research on their therapeutic potential and the understanding of their mechanism of action is still taking its first steps, and there is a distinct lack of research in the parasitology field. In the present work, we describe the synthesis and physical properties of seven new lanthanide complexes with the anionic form of the bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO), namely [Ln(mtpO)3(H2O)6]·9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III), Dy(III) and Er(III)). In addition, results on the in vitro antiproliferative activity against Leishmania spp. and Trypanosoma cruzi are described. The high activity of the new compounds against parasite proliferation and their low cytotoxicity against reference host cell lines show a great potential of this type of compounds to become a new generation of highly effective and non-toxic antiparasitic agents to fight the so considered neglected diseases leishmaniasis and Chagas disease.
authors.affiliation: Departamento de Química Inorgánica, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain. Electronic address: ana.caballero@qi.ub.es.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Caballero
authors.affiliation: Departamento de Química Inorgánica, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Diéguez
authors.affiliation: Departamento de Química Inorgánica, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Salas
authors.affiliation: Departamento de Parasitología, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
authors.affiliation: Departamento de Parasitología, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Marín
authors.affiliation: Departamento de Parasitología, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ramírez-Macías
authors.affiliation: Departamento de Química Inorgánica, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Santamaría-Díaz
authors.affiliation: Departamento de Estadística, Universidad de Granada, Severo Ochoa s/n, 18071 Granada, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Gutiérrez-Sánchez
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy*; D002522:Chlorocebus aethiops; D056831:Coordination Complexes; D018360:Crystallography, X-Ray; D005260:Female; D020128:Inhibitory Concentration 50; D028581:Lanthanoid Series Elements / Q000737:chemistry / Q000627:therapeutic use*; D007891:Leishmania / Q000187:drug effects; D007892:Leishmania braziliensis / Q000187:drug effects; D018314:Leishmania infantum / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy*; D008024:Ligands; D011744:Pyrimidinones / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D014230:Triazoles / Q000737:chemistry* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects; D014709:Vero Cells
chemical_list: C000595548:5-methyl-1,2,4-triazolo(1,5-a)pyrimidin-7(4H)-one; D000981:Antiprotozoal Agents; D056831:Coordination Complexes; D028581:Lanthanoid Series Elements; D008024:Ligands; D011744:Pyrimidinones; D014230:Triazoles
keywords: Antiparasitic; Leishmania; Triazolopyrimidine; Trypanosoma