CNR ExploRA

Articolo in rivista, 2023, ENG

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

Eoin Moynihan 1, Silvia Panseri 2 , Giada Bassi 2,3 , Arianna Rossi 2,4 , Elisabetta Campodoni 2 , Eithne Dempsey 1,5, Monica Montesi 2,* , Trinidad Velasco-Torrijos 1,5 and Diego Montagner 1,5,*

1 Department of Chemistry, Maynooth University, W23 F2H6 Maynooth, Ireland 2 Institute of Science, Technology and Sustainability for Ceramics, National Research Council (CNR), 48018 Faenza, Italy 3 Department of Neuroscience, Imaging and Clinical Sciences, University of Studies "G. D'Annunzio", 66100 Chieti, Italy 4 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy 5 Kathleen Londsdale Institute for Human Health Research, Maynooth University, W23 F2H6 Maynooth, Ireland

Despite the enormous importance of cisplatin as a chemotherapeutic agent, its application is impacted by dose-limiting side effects and lack of selectivity for cancer cells. Researchers can overcome these issues by taking advantage of the pro-drug nature of the platinum(IV) oxidation state, and by modifying the coordination sphere of the metal centre with specific vectors whose receptors are overexpressed in tumour cell membranes (e.g., carbohydrates). In this paper we report the 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 common in adolescents and young adults. The carbohydrate-targeting vectors and Pt scaffold are linked using copper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry, which is synonymous with mild and robust reaction conditions. The novel complexes are characterised using multinuclear 1D-2D NMR (1H, 13C and 195Pt), IR, HR-MS, Elem. Analyses, and CV. Cytotoxicity on 2D and 3D and cell morphology studies on OS cell lines, as well as non-cancerous human foetal osteoblasts (hFOBs), are discussed.

International journal of molecular sciences (Online)