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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00511667" target="_blank" >RIV/68081707:_____/19:00511667 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlepdf/2019/sc/c9sc02651g" target="_blank" >https://pubs.rsc.org/en/content/articlepdf/2019/sc/c9sc02651g</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c9sc02651g" target="_blank" >10.1039/c9sc02651g</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10405 - Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemical Science

ISSN

2041-6520

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

37

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

8547-8557

Kód UT WoS článku

000487674500002

EID výsledku v databázi Scopus

—