PubReading [43] - Click and Cut: a click chemistry approach to developing oxidative DNA damaging agents - N. McStay, A. Kellett et al.

Metallodrugs provide important first-line treatment against various forms of human cancer. To overcome chemotherapeutic resistance and widen treatment possibilities, new agents with improved or alternative modes of action are highly sought after. Here, we present a click chemistry strategy for developing DNA damaging metallodrugs. The approach in- volves the development of a series of polyamine ligands where three primary, secondary or tertiary alkyne-amines were selected and ‘clicked’ using the copper-catalysed azide-alkyne cycloaddition reac- tion to a 1,3,5-azide mesitylene core to produce a family of compounds we call the ‘Tri-Click’ (TC) se- ries. From the isolated library, one dominant ligand (TC1) emerged as a high-affinity copper(II) binding agent with potent DNA recognition and damaging  ...