Abstract
Click chemistry is fundamentally important to medicinal chemistry and chemical biology. It represents a powerful and versatile tool, which can be exploited to develop novel Pt-based anticancer drugs and to better understand the biological effects of Pt-based anticancer drugs at a cellular level. Innovative azide–alkyne cycloaddition–based approaches are being used to functionalise Pt-based complexes with biomolecules to enhance tumour targeting. Valuable information in relation to the mechanisms of action and resistance of Pt-based drugs is also being revealed through click-based detection, isolation and tracking of Pt drug surrogates in biological and cellular environments. Although less well-explored, inorganic Pt-click reactions enable synthesis of novel (potentially multimetallic) Pt complexes and provide plausible routes to introduce functional groups and monitoring Pt-azido drug localisation.
Highlights
Of the cancer patients who are treated with chemotherapy, around 50% receive a Pt(II)-based medicine such as cisplatin, carboplatin or oxaliplatin (Figure 1a) [1]
Azideealkyne organic click reactions have been used to prederivatise the ligands of Pt complexes, to include targeting agents and fluorophores
A series of Pt complexes containing ligand-based azide or alkyne click handles have been validated as important templates for functionalisation with complementary partners
Summary
Of the cancer patients who are treated with chemotherapy, around 50% receive a Pt(II)-based medicine such as cisplatin, carboplatin or oxaliplatin (Figure 1a) [1]. Pt(II) anticancer drugs react with a range of other nucleophiles, including RNA, mitochondrial DNA and proteins [2,3]. Oxaliplatin is used clinically to treat stage III colorectal cancer and exhibits a fundamentally different cytotoxic profile to cisplatin and carboplatin. DNA platination does occur, other effects including induction of immunogenic cell death [1,4] and ribosome biogenesis stress are thought to dominate the anticancer mechanism of action of oxaliplatin [5]. CuAAC has been used to develop triazole-based ligands [10*,15], and for chemical conjugations including for labelling in biological systems, though reactions in living systems are limited by Cu(I)-associated toxicity [16]
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