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

0511667 - BFÚ 2020 RIV GB eng J - Článek v odborném periodiku
Song, H. - Rogers, N.J. - Allison, S.J. - Brabec, Viktor - Bridgewater, H. - Kostrhunová, Hana - Marková, Lenka - Phillips, R.M. - Pinder, E.C. - Shepherd, S.L. - Young, L.S. - Zajac, Juraj - Scott, P.
Discovery of selective, antimetastatic and anti-cancer stem cell metallohelices via post-assembly modification.
Chemical Science. Roč. 10, č. 37 (2019), s. 8547-8557. ISSN 2041-6520. E-ISSN 2041-6539
Grant CEP: GA ČR(CZ) GA17-05302S; GA MŠMT(CZ) LTC17003
Institucionální podpora: RVO:68081707
Klíčová slova: liver metastasis * cancer * peptides * complexes
Obor OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis)
Impakt faktor: 9.346, rok: 2019
Způsob publikování: Omezený přístup
https://pubs.rsc.org/en/content/articlepdf/2019/sc/c9sc02651g

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.
Trvalý link: http://hdl.handle.net/11104/0301895