## 5 Gold Based Carbene Complexes  
Heterocyclic and metallocene complexes have also been investigated for their potential antitumor activity [67; 68; 69]. These metal complexes have the general formula L\({}_{\text{n}}\)MX\({}_{\text{m}}\), where M is the metal that constitutes the reactive center, in its oxidation state equal to 0, L is the carbene, which is the ligand able to influence the electronic properties of the metal and consequently, the possible catalytic activity of the complex and X is a non-carbenic ligand of anionic nature, such as a halide, a carboxylate or an alkoxide [70; 71]. The stability and chemical reactivity of these complexes can be influenced by the covalent bonds coordinated with various transition metal centers through \(\sigma\) donation and \(\pi\)-retro-donation, the aromaticity of the NHC ligand and the volume of the side chains [72]. Among these, heterocyclic gold \(N\)-carbene (NHC) complexes attract particular interest in the pharmaceutical research sector, meeting the requirements for efficient and rapid drug design, and for thence to their chemical stability [73]. A number of gold NHC complexes have been biologically tested and, in particular, some of them have also shown anticancer effects in vitro. Au-NHC complexes offer a wide range of biological activities, such as antiarthritic [74], antimicrobial [75] and especially antitumor ones. The anticancer properties of Au (I/III)-NHC complexes have been studied in different cellular backgrounds, such as melanoma, breast, prostate and hepatocellular carcinoma cell lines. It has been shown that Au-NHC complexes can differently affect cell cycle distribution, expressions of several key regulators of apoptosis, mitochondrial integrity, activation of caspases and generation of reactive intracellular oxygen species (ROS) [76]. The structures of these gold NHC complexes were synthesized to evaluate the influence of increased lipophilicity on their pharmacological effects [77]. The lipophilic cation, whose \(\pi\)-electrons are delocalized, can cross biological membranes more rapidly and concentrate within the mitochondria of cancer cells. The lipophilicity of the complex increases when the nitrogen atoms are functionalized with lipophilic substituents. The effect of different substituents on the N-1 atom on pharmacological activity was tested. In particular, position 1 was functionalized with 2-cyclopentanol (L1), 2-cyclohexanol (L2) and 2-hydroxy-2-phenylethyll (L3) while in position 3 a methyl group was always present (Figure 7). The obtained complexes were studied for their anticancer properties against human breast cancer cells and the underlying molecular mechanism was studied in detail by biological assays and macromolecular docking studies, in order to understand the probable ligand-protein binding modes. One of the tested compounds, AuL3, showed good  
Figure 6: Molecular structure of the gold (III) thiosemicarbazone (**8**). growth inhibitory activity by inducing apoptosis of breast cancer cells, without exerting any effect on healthy breast epithelial cells. The antitumor activity of these complexes was evaluated on two breast cancer cell lines, MCF-7 and MDA-MB-231. The results obtained highlighted an interesting antitumor activity of the compounds shown in Figure 8, in particular on the highly aggressive and metastatic MDA-MB-231 cell line. In vitro studies have shown that these compounds are able to interfere with tubulin polymerization by inhibiting the activity of hTopo I and II, already at the minimum concentration of 1 M. Therefore, these results have shown that these compounds may be useful for further future investigations enabling the development of new multitarget agents in the treatment of breast cancer. Antiarthritic Gold Compounds in OncologyThe treatment of different tumors with _cis_platin, (NH3)2 PCl2, has initiated and focused the pharmacological research towards metal-based drugs, such as gold (I, III) compounds, in particular, those that exhibit antiarthritic, antitumor and cytotoxic activity.