Anticancer Activity and Structural Investigations of Novel Carbonyl Diphosphine Ruthenium(II) Complexes

The aim of this thesis was the synthesis of novel ruthenium complexes and the evaluation of their anticancer activity. Moreover, the behavior of these systems in water solution and towards different substrates was deeply studied. The work performed on this subject can be divided into four parts as follows: 1. The first part has concerned the synthesis and the characterization of three neutral ruthenium complexes of general formula [Ru(η1-OAc)(CO)(dppb)(dkt)] (dkt = acetylacetonate, dibenzoylmethane, curcumin), trying to exploit the β-diketones properties as antioxidant, anti-inflammatory, anticarcinogenic and chemopreventive agents. 2. The second part has been focused on the synthesis and characterization of monocationic ruthenium complexes bearing diimine ligands in place of β-diketones. Once obtained the complex of formula [Ru(η1-OAc)(CO)(dppb)(phen)]OAc and studied its reactivity, precise and rationalized modification on the ligands around the ruthenium center have been carried out, including phenanthroline functionalization, substitution of different anions, introduction of chiral diphosphines and replacement of the carbonyl with an isonitrile group. All these modifications were carried out after structure-activity relationship (SAR) evaluations. 3. During the third part, dicationic ruthenium complexes of general formula [Ru(CO)(dppb)(phen)(L)](PF6)2 (L = 1,3,5-triaza-7-phosphaadamantane or pyridine) have been obtained exploiting a protic solvent like water, starting from [Ru(η1-OAc)(CO)(dppb)(phen)]OAc. 4. The final part has regarded the evaluation of the anticancer activity of the novel ruthenium complexes against anaplastic thyroid cancer and colon carcinoma cell lines. In addition, for the most promising complexes, the capacity to induce apoptotic cell death and the antimetastatic properties were studied.