## 2 Metal-Based Carbohydrate Drug Conjugates
The desired complexes **16a-b**, **17a-b** and **18a-b** were successfully obtained as a mixture of four diastereoisomers and then tested as potential anticancer agents (Figure 4). Figure 3: (**A**) Gold complexes reported by [PERSON], [PERSON] and [PERSON]; (**B**) Silver complexes described by [PERSON], [PERSON] and [PERSON]. It is noteworthy to mention that the very low IC\({}_{50}\) values obtained on A2780, A2780_cis_, OVCAR-5, A549, A375, KURAMOCHI and OVCAR-3 cells have demonstrated the successful design of the compounds. More specifically, all IC\({}_{50}\) values are in the low micromolar range and in all cases lower than cisplatin. The similar IC\({}_{50}\) values obtained on A2780 and A2780_cis_ (cisplatin-resistant clone) cell lines, suggest the different mechanism of action of these Pd-NHC complexes with respect to cisplatin. The highest cytotoxicity was observed in the case of complex **17a**, whereas the lowest activity was observed in the case of complex **17b**. Interestingly, the Pd complexes bearing PTA combine a good cytotoxicity towards cancer cells with a poor cytotoxicity towards normal ones (MRC-5 fibroblasts) [67]. Moving to Group 8 of the Periodic Table, some interesting works dealing with the anticancer properties of iron, ruthenium and osmium complexes bearing glycosidic moieties have been published in the last three years [68; 69; 70]. In particular, ruthenium complexes are widely studied as chemotherapeutic agents as well as efficient photosensitizers for photodynamic therapy. Considering the glycosidic derivatives, Ru(II) \(p\)-cymene phosphate complexes depicted in Figure 5A have been recently synthesized, focusing on 2,3 unsaturated hexoses (compounds **19** and **20**) and glucose derivatives (compounds **21** and **22**). All the synthesized complexes have been tested towards ovarian and breast cancer cell lines (A2780, A2780_cis_ and MCF7), showing a moderate-to-good antiproliferative activity only in the case of complexes **19\(\alpha\)** and **19\(\beta\)** (IC\({}_{50}\) = 2-20 uM). More specifically, the \(\beta\) isomer exhibited a superior activity compared to its \(\alpha\) congener, but without a significant selectivity. In addition, these two Ru(II) complexes seem to act with different mechanisms of action. Complex **19\(\beta\)** showed a remarkable accumulation of treated cells in S and G2/M phases. Conversely, complex **19\(\alpha\)** showed no alteration of the cell cycle. Although both complexes induced oxidative stress (ROS production), only complex **19\(\beta\)** can activate Caspases 3/7 and damage the mitochondria membrane [68]. Figure 4: Pd(II)-allyl complexes bearing glucosidic-NHC ligands. A panel of cationic half-sandwich Ru(II) \(p\)-cymene complexes have been prepared by [PERSON] and [PERSON] (see Figure 5B), and the key role of the ancillary ligands in the cytotoxicity has been demonstrated [69]. In particular, complexes **23-26** showed IC\({}_{50}\) values in the micromolar range (0.9-9 uM) on A2780 and ID8 ovarian cancer cell lines. Interestingly, the best candidates exhibited a very low cytotoxicity on normal cells (MRC-5 fibroblasts), thus demonstrating an interesting selectivity. Curiously, the use of deprotected sugars is sufficient to suppress the anticancer properties of the complexes. More in general, the increase in lipophilicity of the sugar moiety improves the cytostatic properties and induces a cooperative binding to unidentified targets with a remarkable ROS production. With the aim of investigating the role of the metal centre, [PERSON] and [PERSON] have reported the synthesis of osmium complexes **27** and **28** bearing the same ligands used in the previously mentioned ruthenium derivatives (Figure 5B). The biological tests have shown a lower cytotoxicity of osmium complexes compared to their ruthenium congeners [70]. Iron complexes, especially ferrocenyl derivatives, are well known as potent antimalarial, antifungal and anticancer agents.