## 4 Gold Complexes  
In recent decades, new gold complexes have been developed with antibacterial, antiviral, antiparasitic and antitumor activity [60]. Several intracellular protein targets, such as kinases, reductases, proteases and topoisomerases, interact with gold (III) complexes; in particular, the blocking of the latter leads to programmed cell death [61]. The ability of [Au(C'N'C)(IME)]CF\({}_{3}\)SO\({}_{3}\) (**1**) (Figure 3) to inhibit the relaxation reaction of supercoiled DNA was analyzed. By comparing the different electrophoretic mobility of both supercoiled and relaxed forms, it was shown that compound **1** was able to inhibit the relaxation activity of human IB topoisomerase. A study conducted in 2012 described the use of oxoglaucine (OG) as a ligand, an alkaloid extract of oxoaporphine obtained from the overground parts of different plants, such as Annonaceae, Magnoliaceae and Papaveraceae [62]. The reaction was carried out between OG and a gold (III) salt, to obtain the complex of gold (III) (**2**), an ionic compound made up of the oxoglaucine cation and the anion [AuCl\({}_{4}\)]- having a square planar structure (Figure 3). In this compound, the oxoglaucine is protonated on the nitrogen atom while the gold (III) tetrachloride acts as a counter ion, balancing the charge. Crystallographic data confirmed that oxogalucine organizes itself into a planar structure, capable of intercalating DNA [63]. The ability of compound **2** to block tumor growth was evaluated in vitro against different cell lines where the best results were obtained for human papillomavirus-related endocervical adenocarcinoma BEL7404 cells, with an inhibitory concentration IC\({}_{50}\) (i.e., the half maximal inhibitory concentration) of 6.1 \(\pm\) 0.5 uM and for AS49 human lung carcinoma cells (IC\({}_{50}\) = 1.4 \(\pm\) 0.7 uM) [62]. Figure 4 shows the square planar gold (III) chelates (**3**-**6**), synthesized by [PERSON] et al. [64], in which the pyridyl- or issoquinolylamide bidentate anionic chelators are used as ligands, in order to stabilize gold (III) through the presence of donor \(\sigma\) atoms. Among these, only compound **6** showed a good cytotoxic profile, towards two ovarian cancer cells (OVCAR-3 and IGROV1, with IC\({}_{50}\) values of 4.0 and 9.8 uM, respectively) and against one colon tumor cell line (SW-620, IC\({}_{50}\) = 15 uM). Compound **6** is both a topoisomerase IIa (TopoIIa) inhibitor, with a mechanism of action similar to that of zorubicin, and a TopolB inhibitor, such as Topotecan and 9-methoxycampotthecin. Furthermore, this compound is structurally similar to _cis_platin, but does not possess the same anticancer properties, probably due to the fact that the chloride ligands are not reactive. This condition could inhibit the replacement of water with the metal ion in vivo and the consequent formation of a gold (III)-DNA complex. Another study described the biological properties of a series of planar cationic Au\({}^{3+}\) macrocycles containing two pyrrole-imine units linked to a quinoxaline group and an alkyl chain. Among these molecules, shown in Figure 5, compound **7** showed the best antiproliferative activity, against different types of cell lines. Moreover, it exhibits a marked inhibition activity of Topol at 500 nM  
Figure 3: Molecular structure of [Au(C’N’C)(IME)]CF\({}_{3}\)SO\({}_{3}\)] (**1**) and [OGH][AuCl\({}_{4}\)] (**2**) [60]. Abbreviations: C’N’C is the bi-cyclometallated di-anionderived from 2,6-diphenylpyridine, IMe is \(N\),\(N^{\prime}\)-dimethylimidazolium and [OGH](+) is the charged alkaloid oxoglaucine (OG). and a total inhibitor at the dose of 5 \(\upmu\)M. In particular, the presence of gold (III) is crucial for the inhibition of topoisomerase and for DNA intercalation [65]. Another study, conducted in 2016, ref. [66] focused on the synthesis of thiosemicar-bazones coordinated with different metals (Pt, Pd and Au).