Discovery of selective, antimetastatic and anti-cancer stem cell metallohelices via post-assembly modification

Hualong Song, Nicola Rogers, Simon J. Allison, Viktor Brabec, Hannah Bridgewater, Hana Kostrhunova, Lenka Markova, Roger Phillips, Emma Pinder, Samantha Shepherd, Lawrence Young, Juraj Zajac, Peter Scott

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Helicates and related metallofoldamers, synthesised by dynamic self-assembly, represent an area of chemical space inaccessible by traditional organic synthesis, and yet with potential for discovery of new classes of drug. Here we report that water-soluble, optically pure Fe(ii)- A nd even Zn(ii)-based triplex metallohelices are an excellent platform for post-assembly click reactions. By these means, the in vitro anticancer activity and most importantly the selectivity of a triplex metallohelix Fe(ii) system are dramatically improved. For one compound, a remarkable array of mechanistic and pharmacological behaviours is discovered: Inhibition of Na +/K + ATPase with potency comparable to the drug ouabain, antimetastatic properties (including inhibition of cell migration, re-adhesion and invasion), cancer stem cell targeting, and finally colonosphere inhibition competitive with the drug salinomycin.

Original languageEnglish
Pages (from-to)8547-8557
Number of pages11
JournalChemical Science
Issue number37
Early online date18 Jul 2019
Publication statusPublished - 7 Oct 2019


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