Exploiting azide–alkyne click chemistry in the synthesis, tracking and targeting of platinum anticancer complexes

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.

Graphical abstract

Highlights

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  Click chemistry is integral to the chemical biology of Pt anticancer complexes.

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  The Cu(I)-catalysed [3 + 2] azide–alkyne cycloaddition (CuAAC)/strain-promoted [3 + 2] azide–alkyne cycloaddition (SPAAC) enable the functionalisation of Pt drug candidates.

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  CuAAC/SPAAC aid the detection, isolation and tracking of Pt drugs.

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  CuAAC/SPAAC facilitate the development of novel Pt triazole–based complexes.