Mo(II) complexes: A new family of cytotoxic agents?


Several molybdenum complexes, [Mo(eta(3)-C(3)H(5))X(CO)(2)(N-N)] (N-N= 1,10-phenanthroline, phen: X= CF(3-) SO(3) Ti, X= Br Bl, X =Cl C1; N-N=2,2 '-bipyridyl, X= CF(3)SO(3) T2, X = Br B2) and [W(eta(3)-C(3)H(5))Br(CO)(2) (phen)1 (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, MTV), leading to IC(50) values ranging from 3 to 45 mu M, approximately. Most complexes exhibited significant antitumoral activity. Complexes B1 and 12 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 12 exhibit a selective uptake by cells and intermediate partition coefficients. The binding constants of B1 and 12 with ct DNA, as determined by absorption titration, are 2.08 ( +/- 0.98) x 105 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. (C) 2010 Elsevier Inc. All rights reserved.




Biochemistry & Molecular Biology; Chemistry


Bandarra, D; Lopes, M; Lopes, T; Almeida, J; Saraiva, MS; Vasconcellos-Dias, M; Nunes, CD; Felix, V; Brandao, P; Vaz, PD; Meireles, M; Calhorda, MJ

nossos autores


The authors are grateful to F. Antunes (FCUL) for providing the cell lines and to F. Martins (FCUL) for inestimable help in octanol partition studies. The authors thank the Portuguese National Mass Spectrometry Network (REDE/1501/REM/2005). MSS (SFRH/BD/48640/2008) thanks FCT for a research grant.

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