title: Vanadium polypyridyl compounds as potential antiparasitic and antitumoral agents: new achievements.
abstract: In the search for new therapeutic tools against diseases produced by kinetoplastid parasites five vanadyl complexes, [V(IV)O(L-2H)(phen)], including 1,10-phenanthroline (phen) and tridentate salicylaldehyde semicarbazone derivatives as ligands have been synthesized and characterized in the solid state and in solution by using different techniques. EPR suggested a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and phen coordinated in an equatorial/axial mode. The compounds were evaluated in vitro on epimastigotes of Trypanosoma cruzi, causative agent of Chagas disease, Leishmania panamensis and Leishmania chagasi and on tumor cells. The complexes showed higher in vitro anti-trypanosomal activities than the reference drug Nifurtimox (IC(50) values in the range 1.6-3.8 μM) and increased activities in respect to the free semicarbazone ligands. In vitro activity on promastigote and amastigote forms of Leishmania showed interesting results. The compounds [VO(L1-2H)(phen)] and [VO(L3-2H)(phen)], where L1 = 2-hydroxybenzaldehyde semicarbazone and L3 = 2-hydroxy-3-methoxybenzaldehyde semicarbazone, resulted active (IC(50) 2.74 and 2.75 μM, respectively, on promastigotes of L. panamensis; IC(50) 19.52 and 20.75 μM, respectively, on intracellular amastigotes of L. panamensis) and showed low toxicity on THP-1 mammalian cells (IC(50) 188.55 and 88.13 μM, respectively). In addition, the complexes showed cytotoxicity on human promyelocytic leukemia HL-60 cells with IC(50) values of the same order of magnitude as cisplatin. The interaction of the complexes with DNA was demonstrated by different techniques, suggesting that this biomolecule could be a potential target either in the parasites or in tumor cells.
authors.affiliation: Facultad de Química, UDELAR, Gral. Flores 2124, 11800 Montevideo, Uruguay.
authors.forename: Julio
authors.initials: J
authors.lastname: Benítez
authors.forename: Lorena
authors.initials: L
authors.lastname: Becco
authors.forename: Isabel
authors.initials: I
authors.lastname: Correia
authors.forename: Sandra Milena
authors.initials: SM
authors.lastname: Leal
authors.forename: Helena
authors.initials: H
authors.lastname: Guiset
authors.forename: João Costa
authors.initials: JC
authors.lastname: Pessoa
authors.forename: Julia
authors.initials: J
authors.lastname: Lorenzo
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tanco
authors.forename: Patricia
authors.initials: P
authors.lastname: Escobar
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garat
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004270:DNA, Circular / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects; D014639:Vanadium
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004270:DNA, Circular; D014344:Trypanocidal Agents; D014639:Vanadium; D004247:DNA; C427203:calf thymus DNA