Studies of interaction of dichloro[eta2-dimethyl-(2-methylidene-cyclohexylmethyl)-amino]platinum(II) with DNA: effects on secondary and tertiary structures of DNA - cytotoxic assays on human cancer cell lines Capan 1 and A431.
The interaction with DNA and the cytotoxic activity of a new organometallic platinum(II) compound were studied. Different techniques were used to evaluate changes in secondary and tertiary DNA structures, and to obtain images of DNA morphological changes. The ability of platinum complex to modify secondary DNA structure was explored by circular dichroism (CD). Electrophoretic mobility showed changes in tertiary DNA structure. Finally, Atomic Force Microscopy (AFM) revealed morphological changes of plasmid DNA (pBR322). This compound breaks the traditional structure-activity rules for cis-platinum compounds, but it could be of interest because of its different kinetics. An organometallic bond normally shows a higher trans-effect than an amine ligand, and that fact, a priori, could contribute to a higher DNA binding rate. Human A431 and Capan-1 cells (vulvae carcinoma and pancreatic carcinoma, respectively) were exposed to increasing concentrations of cisplatin and complex 6 for 24 h, after which time the cell number/viability was determined by the colorimetric MTT assay. A low cytotoxicity of organometallic compound 6 against A431 and Capan-1 cancer cell lines was observed and this result is consistent with the low interaction with DNA observed in previous studies.