title: Hydroxyquinoline derived vanadium(IV and V) and copper(II) complexes as potential anti-tuberculosis and anti-tumor agents.
abstract: Several mixed ligand vanadium and copper complexes were synthesized containing 8-hydroxyquinoline (8HQ) and a ligand such as picolinato (pic(-)), dipicolinato (dipic(2-)) or a Schiff base. The complexes were characterized by spectroscopic techniques and by single-crystal X-ray diffraction in the case of [V(V)O(L-pheolnaph-im)(5-Cl-8HQ)] and [V(V)O(OMe)(8HQ)2], which evidenced the distorted octahedral geometry of the complexes. The electronic absorption data showed the presence of strong ligand to metal charge transfer bands, significant solvent effects, and methoxido species in methanol, which was further confirmed by (51)V-NMR spectroscopy. The structures of [Cu(II)(dipic)(8HQ)]Na and [V(IV)O(pic)(8HQ)] were confirmed by EPR spectroscopy, showing only one species in solution. The biological activity of the compounds was assessed through the minimal inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis (Mtb) and the cytotoxic activity against the cisplatin sensitive/resistant ovarian cells A2780/A2780cisR and the non-tumorigenic HEK cells (IC50 values). Almost all tested vanadium complexes were very active against Mtb and the MICs were comparable to, or better than, the MICs of drugs, such as streptomycin. The activity of the complexes against the A2780 cell line was dependent on incubation time presenting IC50 values in the 3-14 μM (at 48 h) range. In these conditions, the complexes were significantly (*P<0.05-**P<0.001) more active than cisplatin (22 μM), in the A2780 cells and even surpassing its activity in the cisplatin-resistant cells A2780cisR (2.4-8 μM vs. 75.4; **P<0.001). In the non-tumorigenic HEK cells poor selectivity toward cancer cells for most of the complexes was observed, as well as for cisplatin.
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Correia
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Adão
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Somnath
authors.initials: S
authors.lastname: Roy
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; Inorganic Chemistry Dep., National Research Center, El Buhouth St., Dokki, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Wahba
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Matos
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India.
authors.forename: Mannar R
authors.initials: MR
authors.lastname: Maurya
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10,km 139.7, 2695-066 Bobadela LRS, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP, C.P. 582, Araraquara, SP 14801-902, Brazil.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP, C.P. 582, Araraquara, SP 14801-902, Brazil.
authors.forename: Clarice Q F
authors.initials: CQF
authors.lastname: Leite
authors.affiliation: Departamento de Química Fundamental, Universidade da Coruña, Campus de A Zapateira, 15071 A Coruña, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Avecilla
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: joao.pessoa@ist.utl.pt.
authors.forename: João
authors.initials: J
authors.lastname: Costa Pessoa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D010848:Picolinic Acids / Q000737:chemistry; D012545:Schiff Bases / Q000737:chemistry; D013329:Structure-Activity Relationship; D014639:Vanadium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D056831:Coordination Complexes; D006912:Hydroxyquinolines; D010848:Picolinic Acids; D012545:Schiff Bases; D014639:Vanadium; D003300:Copper; D002945:Cisplatin
keywords: 8-Hydroxyquinoline; Copper complexes; Cytotoxicity; Tuberculosis; Vanadium complexes