Mo(II) complexes: a new family of cytotoxic agents?
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.
Bandarra
Daniel
D
Departamento de Química e Bioquímica, CQB, Faculdade de Ciências, Universidade de Lisboa, Campo Grande 1749-016 Lisboa, Portugal.
Lopes
Miguel
M
Lopes
Telma
T
Almeida
Joana
J
Saraiva
Marta S
MS
Vasconcellos-Dias
Maria
M
Nunes
Carla D
CD
Félix
Vitor
V
Brandão
Paula
P
Vaz
Pedro D
PD
Meireles
Margarida
M
Calhorda
Maria José
MJ
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
D000970:Antineoplastic Agents; D010618:Phenanthrolines; D013778:Tetrazolium Salts; D013844:Thiazoles; D014867:Water; D008982:Molybdenum; C022616:thiazolyl blue; D020003:1-Octanol; C025205:1,10-phenanthroline