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

Several molybdenum complexes, [Mo(eta(3)-C3H5)X(CO)(2)(N-N)] (N-N= 1,10-phenanthroline, phen: X= CF3- SO3 Ti, X= Br Bl, X =Cl C1; N-N=2,2 '-bipyridyl, X= CF3SO3 T2, X = Br B2) and [W(eta(3)-C3H5)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 IC50 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.