## 2 Metal-Based Carbohydrate Drug Conjugates  
Glyolysis is the first key step of the glucose metabolism. More specifically, one molecule of glucose is degraded, under anaerobic conditions, by a cascade of enzymatic reactions in two molecules of pyruvate with production of ATP (Adenosine Tri-Phosphate). In the absence of oxygen, pyruvate evolves into lactate or ethanol (fermentation). On the contrary, in the presence of oxygen, pyruvate is involved in the Krebs cycle for the respiration process. The latter, in conjunction with the oxidative phosphorylation, takes place in the mitochondria and produces a lot of energy compared to glycolysis. Cancer cells, with their altered metabolism, do not exploit the traditional Krebs cycle/mitochondrial oxidative phosphorylation pathway as an energy source, even under aerobic conditions. The inefficient metabolism of cancer cells is based on a different mechanism, known as aerobic glycolysis, to produce the ATP necessary for their growth and proliferation. This phenomenon is called _Warburg Effect_, which is characterized by a higher uptake and consumption of glucose by cancer cells compared to normal ones [45]. As a consequence, the massive production of lactate from the aerobic glycolysis is responsible for the acidic pH of the tumour microenvironment. Many studies have demonstrated the role of the _Warburg Effect_ in the oncogenesis process as well as the ability of this abnormal glucose metabolism to induce the resistance of cancer cells towards classical chemotherapy. Additional details on how aerobic glycolysis, tumour microenvironment and signalling pathways affect the cancer therapy are well summarized by [PERSON] in a recent review [46]. Taking advantage of the _Warburg Effect_, many research groups have employed glucose and its derivatives to develop analytical techniques aimed at identifying tumour masses (e.g., Positron Emission Tomography, PET) and/or to design selective anticancer drugs. In particular, the introduction of a glycosidic moiety in the chemical structure of a metal complex can, in theory, increase the uptake on cancer cells and the selectivity of the metallodrug. In addition, carbohydrate moieties can be used to improve the solubility of metal complexes in the biological media and can act as efficient drug delivery systems, especially in the case of cyclodext derivatives [47]. In this context, a comprehensive review dealing with carbohydrate-metal complexes with interesting anticancer properties was assembled by [PERSON] and colleagues in 2020 [48], covering all the contributions published in this area until 2019. In the last three years, the [PERSON] group investigated the synthesis and antitumor activity of a selection of platinum glycoconjugated complexes with different geometries and oxidation states of the metal centre [49; 50; 51]. In particular, the authors prepared in good yields and purity the platinum(0) complex (**1**) shown in Figure 1A, which bears a glycoconjugated 2-iminopyrydine and dimethylfumarate. This olefin ligand is currently used for the treatment of multiple sclerosis. The high degree of metal-to-olefin \(\pi\)-backdonation permits a parallelism with square planar Pt(II) complexes owing to the metallacyclopropanecharacter of these formal Pt(0) species. The synthesized Pt(0) complex is water soluble, and its antiproliferative activity towards two tumoral (A431 and SVT2) and two non-tumoral (BALB/c3T3 and HaCaT) epithelial cell lines was evaluated by MTT assay after 48 h of incubation. The IC\({}_{50}\) values indicate a superior cytotoxicity of this Pt(0) complex with respect to cisplatin in the SVT2 cancer cell line (IC\({}_{50}\) = 61 \(\upmu\)M). However, the similar IC\({}_{50}\) values obtained on cancer and normal cells suggest a poor selective anticancer activity [49]. As we have mentioned in the introduction section, the stability and geometry of metal complexes are strictly related to their cytotoxic effect and mode of action.