Carolina V. Barra

3,5-Dimethyl-1-thiocarbamoylpyrazole and its Pd(II) complexes: Synthesis, spectral studies and antitumor activity

Complexes of the type [PdX2(tdmPz)] {X=Cl-(1), Br-(2); I-(3); SCN-(4); tdmPz=1-thiocarbamoyl-3,5-dimethylpyrazole} have been synthesized and characterized. Compound 1 was formed from the reaction between [PdCl2(CH3CN)2] and 1-thiocarbamoyl-3,5-dimethylpyrazole. Complexes 2, 3 and 4 were obtained by metathesis of the chloro groups from 1 by bromide, iodide and thiocyanate ions, respectively. All the compounds and cisplatin have been tested in vitro by MTT assay for their cytotoxicity against three murine cancer cell lines: mammary adenocarcinoma (LM3 and LMM3) and lung adenocarcinoma (LP07) as well towards normal murine peritoneal exudate cells (PEC). Promising cytotoxic effect against LM3 has been found for 3 showing IC50 equal to 24.5 microM which is comparable to the value obtained for cisplatin (30.3 microM).

Cationic Pd(II) complexes acting as topoisomerase II inhibitors: Synthesis, characterization, DNA interaction and cytotoxicity.

• Cationic palladium compounds were prepared bearing thiosemicarbazide and triphenylphosphine.

Antitumour Complexes and DNA Interactions and their Tools of Analysis: an Approach to Metalointercalators

DNA is considered to be one of the major targets of anticancer drugs. Cisplatin and its analogues exert their activity by forming covalent bonds with the DNA base pairs. However, the DNA structure enables its interaction with metal complexes in many different modes and intercalation is often observed. Particularly, metallointercalators stand out as a class of potential antitumour agents that could circumvent problems such cellular resistance since their mechanism of action is different from that of cisplatin. The interaction complex-DNA can be studied by various techniques, including reaction with guanosine, electrophoretic mobility shift assay (EMSA), viscosity measurements, spectrocphotometric titration for determination of Kb, DNA thermal denaturation and fluorescence spectroscopy.