Development of Novel Pt(IV)-Carbohydrate Derivatives as Targeted Anticancer Agents against Osteosarcoma.

Despite the enormous importance of cisplatin as a chemotherapeutic agent, its applicationis impacted by dose-limiting side effects and lack of selectivity for cancer cells. Researchers canovercome these issues by taking advantage of the pro-drug nature of the platinum(IV) oxidationstate, and by modifying the coordination sphere of the metal centre with specific vectors whosereceptors are overexpressed in tumour cell membranes (e.g., carbohydrates). In this paper we reportthe synthesis of four novel carbohydrate-modified Pt(IV) pro-drugs, based on the cisplatin scaffold,and their biological activity against osteosarcoma (OS), a malignant tumour which is most commonin adolescents and young adults. The carbohydrate-targeting vectors and Pt scaffold are linked usingcopper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry, which is synonymous with mildand robust reaction conditions. The novel complexes are characterised using multinuclear 1D-2DNMR (1H, 13C and 195Pt), IR, HR-MS, Elem. Analyses, and CV. Cytotoxicity on 2D and 3D and cellmorphology studies on OS cell lines, as well as non-cancerous human foetal osteoblasts (hFOBs),are discussed.