## 5 Gold Based Carbene Complexes
The study of the effectiveness of anticancer drugs, e.g., 6-mercaptoethanol and cyclophosphamide, in the treatment of rheumatoid arthritis, derived from their known immunosuppressive and anti-inflammatory actions [78; 79]. This study established a connection between the two therapies, antiarthritic and antitumor. One of the reasons why scientific research has become interested in gold compounds is their square planar geometry, which unites them to platinum in _cis_platin. Gold (III) is isoelectronic with platinum (II) in _cis_platin and also forming similar planar square complexes. Furthermore, the biological environment is generally reducing, so gold (III) compounds can be reduced in vivo to gold (I) and metallic gold. By coordinating bioactive molecules with gold, it is possible to obtain compounds having greater activity and therapeutic effect than uncoordinated molecules. Promising in vitro inhibitory effects of auranofin (Figure 8b) against HeLa cells [80] and subsequent research on its antitumor activity were investigated. The in vitro cytotoxic activity of auranofin, tested on various cell lines, was similar or even greater than _cis_platin (Figure 8a). Figure 7: NH-Carbene proligands L1, L2 and L3, employed in AuL\({}_{n}\) (\(n\) = 1–3) complexes. A good cytotoxic activity was also evaluated in vivo against P388 lymphocytic leukemia implanted in mice [81]. Several gold (I) thiolates have been tested for their anticancer activity. Aurothioglucose (Figure 9a) and aurothiomalate (Figure 9b) inhibited primary tumor growth in mice with [PERSON] carcinoma and reduced lung metastases [81]. Unlike _cis_platin (**6**), aurothiomalate did not exhibit acute toxicity in vivo. The in vitro cytotoxicity of several gold compounds against B16 melanoma and P388 leukemic cells was examined in a study of auranofin and similar compounds [81]. The result shows that a wide variety of gold (I) phosphine thiolates possesses a significant cytotoxic activity. The presence of a phosphine or arsine as a binder has resulted in an increase in cytotoxicity and in vivo antitumor activity against P388 leukemia, compared to other species. The importance of the type of phosphine, used in the binuclear gold (I) compounds containing bidentate phosphines, was tested in vivo against leukemia P388, by systematically varying the nature of the phosphine and keeping the thiolate, R1S-, constant. The most active compound was the one containing (CH3 CH2)[(CH3)2 CH] P (Figure 10a), while the least active one had (C6H5)2P (Figure 10b). Figure 8: Chemical structure of (**a**) _cis_platin and (**b**) auranofin. Figure 9: Chemical structure of (**a**) aurothioglucose and (**b**) sodium aurothiomalate. In summary, it can be stated that the most active class, among the compounds examined, was the one containing both phosphine and thioglucose ligands. The cytotoxicity and antitumor activity of several gold compounds with phosphine binders was tested and proved cytotoxic against B16 melanoma, subcutaneous breast adenocarcinoma, M5076 reticulum cell sarcoma leukemia and P388 and L1210 leukemia [82]. In addition, two new 1-acridin-9-yl-3-methylthiourea complexes Au(I), [Au(ACRTU)2]Cl (**9**) and [Au (ACRTU)(PPh3)]PF6 (**10**), showed submicromolar cytotoxic activity against A2780 ovarian cancer cells and antiproliferative activity, superior to _cis_platin, against some breast cancer cell lines, with a potent antiangiogenic effect. Compound **9** showed the best inhibitory effect, completely relaxing the supercoiled plasmid DNA at the concentration of 12 uM.