title: Vanadium(IV) and copper(II) complexes of salicylaldimines and aromatic heterocycles: Cytotoxicity, DNA binding and DNA cleavage properties.
abstract: Five copper(II) complexes, [Cu(sal-Gly)(bipy)](1), [Cu(sal-Gly)(phen)] (2), [Cu(sal-l-Ala)(phen)] (3), [Cu(sal-D-Ala)(phen)] (4), [Cu(sal-l-Phe)(phen)] (5) and five oxidovanadium(IV) complexes, [V(IV)O(sal-Gly)(bipy)] (6), [V(IV)O(sal-Gly)(phen)] (7), [V(IV)O(sal-l-Phe)(H2O)] (8), [V(IV)O(sal-l-Phe)(bipy)] (9), [V(IV)O(sal-l-Phe)(phen)] (10) (sal=salicylaldehyde, bipy=2,2'-bipyridine, phen=1,10-phenanthroline) were synthesized and characterized, and their interaction with DNA was evaluated by different techniques: gel electrophoresis, fluorescence, UV-visible and circular dichroism spectroscopy. The complexes interact with calf-thymus DNA and efficiently cleave plasmid DNA in the absence (only 2 and 5) and/or presence of additives. The cleavage ability is concentration-dependent as well as metal and ligand-dependent. Moreover, DNA binding experiments show that the phen-containing Cu(II) and V(IV)O compounds display stronger DNA interaction ability than the corresponding bipy analogues. The complexes present cytotoxic activity against human ovarian (A2780) and breast (MCF7) carcinoma cells. Cell-growth inhibition (IC50) of compounds 1, 2 and 5 in human promyelocytic leukemia (HL60) and human cervical cancer (HeLa) cells were also determined. The copper complexes show much higher cytotoxic activity than the corresponding vanadium complexes and the reference drug cisplatin (except for the sal-Gly complexes); namely, the phenanthroline copper complexes 2-5 are ca. 10-fold more cytotoxic than cisplatin and more cytotoxic than their bipyridine analogues.
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: icorreia@tecnico.ulisboa.pt.
authors: Isabel
authors: I
authors: Correia
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors: Somnath
authors: S
authors: Roy
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors: Cristina P
authors: CP
authors: Matos
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Departamento de Química, Bioquímica e Farmácia, Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
authors: Sladjana
authors: S
authors: Borovic
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Departamento de Química, Bioquímica e Farmácia, Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
authors: Nataliya
authors: N
authors: Butenko
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Departamento de Química, Bioquímica e Farmácia, Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
authors: Isabel
authors: I
authors: Cavaco
authors: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7) 2695-066 Bobadela LRS, Portugal.
authors: Fernanda
authors: F
authors: Marques
authors: Institut de Biotecnologia i Biomedicina, Universidad Autonoma Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors: Julia
authors: J
authors: Lorenzo
authors: Departamento de Química Inorgánica, Universitat Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
authors: Alejandra
authors: A
authors: Rodríguez
authors: Departamento de Química Inorgánica, Universitat Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
authors: Virtudes
authors: V
authors: Moreno
authors: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: joao.pessoa@tecnico.ulisboa.pt.
authors: João Costa
authors: JC
authors: Pessoa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D061986:MCF-7 Cells; D017968:Vanadium Compounds / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D017968:Vanadium Compounds; D003300:Copper; D004247:DNA; C427203:calf thymus DNA
keywords: Copper(II); Heterocycles; Metallonucleases; Salicylaldimines; Vanadium(IV)