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

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Abstract

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)- and 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.

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

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Publication details

The article was received on 31 May 2019, accepted on 16 Jul 2019 and first published on 18 Jul 2019


Article type: Edge Article
DOI: 10.1039/C9SC02651G
Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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

    H. Song, N. J. Rogers, S. J. Allison, V. Brabec, H. Bridgewater, H. Kostrhunova, L. Markova, R. M. Phillips, E. C. Pinder, S. L. Shepherd, L. S. Young, J. Zajac and P. Scott, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C9SC02651G

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