title: Mo(II) complexes: a new family of cytotoxic agents?
abstract: Several molybdenum complexes, [Mo(η(3)-C(3)H(5))X(CO)(2)(N-N)] (N-N = 1,10-phenanthroline, phen: X = CF(3)SO(3)T1, X = Br B1, X = Cl C1; N-N = 2,2'-bipyridyl, X = CF(3)SO(3)T2, X = Br B2) and [W(η(3)-C(3)H(5))Br(CO)(2)(phen)] (W1) have been synthesized and characterized. Their antitumor properties have been tested in vitro against human cancer cell lines cervical carcinoma (HeLa) and breast carcinoma (MCF-7) using a metabolic activity test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT), leading to IC(50) values ranging from 3 to 45 μM, approximately. Most complexes exhibited significant antitumoral activity. Complexes B1 and T2 were chosen for subsequent studies aiming to understand their mechanism of action. Cellular uptake of molybdenum and octanol/water partition assays revealed that both B1 and T2 exhibit a selective uptake by cells and intermediate partition coefficients. The binding constants of B1 and T2 with ct DNA, as determined by absorption titration, are 2.08 (± 0.98) × 10(5) and 3.68 (± 2.01)x 10(5)M(-1), respectively. These results suggest that they interact with DNA changing its conformation and possibly inducing cell death, and may therefore provide a valuable tool in cancer chemotherapy.
authors.affiliation: Departamento de Química e Bioquímica, CQB, Faculdade de Ciências, Universidade de Lisboa, Campo Grande 1749-016 Lisboa, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bandarra
authors.forename: Miguel
authors.initials: M
authors.lastname: Lopes
authors.forename: Telma
authors.initials: T
authors.lastname: Lopes
authors.forename: Joana
authors.initials: J
authors.lastname: Almeida
authors.forename: Marta S
authors.initials: MS
authors.lastname: Saraiva
authors.forename: Maria
authors.initials: M
authors.lastname: Vasconcellos-Dias
authors.forename: Carla D
authors.initials: CD
authors.lastname: Nunes
authors.forename: Vitor
authors.initials: V
authors.lastname: Félix
authors.forename: Paula
authors.initials: P
authors.lastname: Brandão
authors.forename: Pedro D
authors.initials: PD
authors.lastname: Vaz
authors.forename: Margarida
authors.initials: M
authors.lastname: Meireles
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Calhorda
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy; D009447:Neuroblastoma / Q000473:pathology; D009690:Nucleic Acid Conformation; D010618:Phenanthrolines / Q000737:chemistry / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D010618:Phenanthrolines; D013778:Tetrazolium Salts; D013844:Thiazoles; D014867:Water; D008982:Molybdenum; C022616:thiazolyl blue; D020003:1-Octanol; C025205:1,10-phenanthroline