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Issue 37, 2019

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

Supplementary files

Article information


Submitted
31 May 2019
Accepted
16 Jul 2019
First published
18 Jul 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 8547-8557
Article type
Edge Article

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, 10, 8547 DOI: 10.1039/C9SC02651G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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