ABSTRACT
The initial employment of di-2-pyridyl ketone azine in 4f metal chemistry has led to a unique ligand transformation; the resulting anionic ligand is able to bridge two Ln(III) ions, affording neutral and cationic dinuclear complexes with interesting properties.
ABSTRACT
The 1 : 2 reaction of [Ti(eta(5)-C(5)H(5))(2)Cl(2)] and AgF in CHCl(3)/H(2)O yielded the fluoro analog [Ti(eta(5)-C(5)H(5))(2)F(2)] (1) in almost quantitative yield (C(5)H(5) is the cyclopentadienyl group). The coordination about the Ti(IV) atom formed by two fluoro ligands and the centroids of the cyclopentadienyl rings is distorted tetrahedral. The compound crystallizes in the orthorhombic space group C2cm. The lattice constants are a = 5.9055(4), b = 10.3021(5), c = 14.2619(9) A, and alpha = beta = gamma = 90 degrees . The complex has been characterized by elemental analyses and spectroscopic (IR, (1)H NMR) data. A structural comparison of the four members of the [Ti(eta(5)-C(5)H(5))(2)X(2)] family of complexes (X = F, Cl, Br, I) is attempted.
ABSTRACT
Metallocene dihalides, which are cyclopentadienyl complexes with the general formula R2MX2 (where R=eta(5)-C5H5, eta(5)-CH3C5H4, eta(5)-SiMe3C5H4 etc.; M=Ti, Zr, Hf, V or Nb; and X=halogen), are highly effective agents against Ehrlich ascites tumour cells and lymphocytic leukaemia. The aim of this study was to evaluate the antitumor activity of the various metallocene dihalides and particularly their effects on cell proliferation of human breast and colon cancer cells. The growth inhibition of the antitumour metallocenes (eta(5)-C5H5)2TiCl2 and (eta(5)-C5H5)2VCl2 and four ring-substituted derivatives in HT-29 (colon cancer) and MCF-7 (breast cancer) cell lines is reported. The results showed that ring-substitution of metallocenes gave similar or even better activity in cell proliferation reduction, in both cell lines, especially in HT-29 and suggested that ring-substitution may enhance the inhibitory activity of the metallocene compound family.
Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Enzyme-Linked Immunosorbent Assay , Humans , Tumor Cells, CulturedABSTRACT
Titanocene dichloride, the most studied metallocene, exhibits antiproliferative activity in a wide spectrum of murine and human tumours. In this article it is demonstrated that titanocene dichloride inhibits tumour gelatinases in a dose-dependent manner. Substrate saturation experiments and the fact that the IC(50) values were increased in correlation with collagen substrate concentrations indicate that the titanocene dichloride induced inhibition is of a competitive type. Titanocene dichloride also specifically inhibits clostridium collagenase and trypsin, particularly when collagens are used as substrates. Binding experiments demonstrate that cyclopentadiene-Ti(IV) moieties, resulting from titanocene dichloride at physiological pH, are bound mainly to different types of collagens and to a lesser extent to casein or bovine serum albumin, forming soluble and stable adducts. These results indicate that titanocene dichloride behaves as a competitive inhibitor against various proteolytic enzymes by binding to the substrate rather than to the enzyme active site. This property may be responsible for the antiangiogenic effect of titanocene dichloride and additionally contributes to its anticancer action.