Synthesis and Characterization of Platinum-Sugar Conjugate for Targeted Delivery to Cancer Cells

Abstract

Although in the clinic for several decades, platinum (Pt) anticancer drugs have severe limitations, including resistance, both acquired and intrinsic, and dose-limiting side effects. In this study, we synthesise a small molecule-based platinum anticancer drug conjugate that is expected to selectively target cancer cells and thereby, on one hand, increase the effective dose of Pt in the tumour cells and potentially reduce the accumulation of the same in healthy tissues and lowering the side effects, thus tackling one of the major limitations of platinum-based chemotherapy. The need for a highly selective platinum anticancer drug led us to synthesise a platinum(II) drug bearing a DACH (DACH =dichloro(1R,2R)-cyclohexane-1,2-amine) non-leaving group and a malonate bearing sugar targeting moiety, namely, carbamoylmannose as leaving group ligand. Based on the cancer targetability of carbamoylmannose unit of naturally occurring anticancer agent bleomycin A5, we hypothesised that the sugar platinum conjugate will enable achieve the desired selectivity to the tumour cells. In this project, a multistep synthetic route to 3-O-Carbamoyl-D-mannose sugar platinum conjugate is developed. All new compounds including the final sugar-platinum conjugate were characterised using various spectroscopic and analytical techniques such as NMR spectroscopy, mass spectrometry, HPLC etc. The future prospect of the project involves studying the cellular uptake mechanism and anticancer potential of the above said platinum-carbamoyl conjugate.