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

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

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
13 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)8547-8557
Number of pages11
JournalChemical Science
Volume10
Early online date18 Jul 2019
DOIs
Publication statusPublished - 7 Oct 2019
Externally publishedYes

Bibliographical note

This article is Open Access Creative Commons BY license.

Fingerprint

Dive into the research topics of 'Discovery of selective, antimetastatic and anti-cancer stem cell metallohelices via post-assembly modification'. Together they form a unique fingerprint.

Cite this