Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F17%3A00475666" target="_blank" >RIV/61388955:_____/17:00475666 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985858:_____/17:00475666 RIV/00209805:_____/17:00077849 RIV/00216208:11310/17:10364241

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.jorganchem.2017.06.005" target="_blank" >http://dx.doi.org/10.1016/j.jorganchem.2017.06.005</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jorganchem.2017.06.005" target="_blank" >10.1016/j.jorganchem.2017.06.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles

Popis výsledku v původním jazyce

A family of ferrocene derivatives of the general formula [Fe(eta(5)-C5H4CH2(p-C6H4)CH2(N-het))(2)] bearing saturated six- and five-membered N-heterocycles (N-het) was prepared. Reactions of the selected complexes with acids (HCl, acetic acid) afforded either the corresponding hydrochlorides or led to deprotection of the functionalized pendant N-heterocycles. The reaction of [{Ru(eta(6)-p-cymene)Cl-2}(2)] with the corresponding cyclopentadienide derivatives afforded cationic ruthenium complexes [Ru(eta(6)-p-cymene)( eta(5)-C5H4CH2(p-C6H4)CH2(N-het))] Cl while ruthenocenes [Ru(eta(5)-C5H4CH2(p-C6H4)CH2(N-het))(2)] were formed as minor byproducts. The prepared complexes (20 examples) were characterized by elemental analysis, melting point, NMR and ESI-MS and the molecular structures of selected ferrocene derivatives were determined by X-ray diffraction analysis. The ferrocene derivatives and the ruthenium complexes were tested in vitro for their cytotoxic properties against three cell lines derived from ovarian cancer (A2780, A2780cis, and SK-OV-3) and against non-tumour embryonic cell line HEK293 (human kidney cells). The most active ferrocene derivatives displayed cytotoxicity in submicromolar and low micromolar concentration against both cisplatin (CisPt) sensitive and resistant cells. The results showed a significant effect of the pendant N-heterocycle on the ferrocene derivative toxicity and selectivity against cancer cells. Ultimately, ferrocene derivatives bearing either piperidine or morpholine groups were proposed to be the most promising substitutes for platinum drugs, as they exhibited comparable or even higher activity (in comparison to CisPt) against cancer cells, whereas these compounds were found to exhibit lower toxicity against embryonic HEK293 cells. (C) 2017 Elsevier B.V. All rights reserved.n

Název v anglickém jazyce

Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles

Popis výsledku anglicky

A family of ferrocene derivatives of the general formula [Fe(eta(5)-C5H4CH2(p-C6H4)CH2(N-het))(2)] bearing saturated six- and five-membered N-heterocycles (N-het) was prepared. Reactions of the selected complexes with acids (HCl, acetic acid) afforded either the corresponding hydrochlorides or led to deprotection of the functionalized pendant N-heterocycles. The reaction of [{Ru(eta(6)-p-cymene)Cl-2}(2)] with the corresponding cyclopentadienide derivatives afforded cationic ruthenium complexes [Ru(eta(6)-p-cymene)( eta(5)-C5H4CH2(p-C6H4)CH2(N-het))] Cl while ruthenocenes [Ru(eta(5)-C5H4CH2(p-C6H4)CH2(N-het))(2)] were formed as minor byproducts. The prepared complexes (20 examples) were characterized by elemental analysis, melting point, NMR and ESI-MS and the molecular structures of selected ferrocene derivatives were determined by X-ray diffraction analysis. The ferrocene derivatives and the ruthenium complexes were tested in vitro for their cytotoxic properties against three cell lines derived from ovarian cancer (A2780, A2780cis, and SK-OV-3) and against non-tumour embryonic cell line HEK293 (human kidney cells). The most active ferrocene derivatives displayed cytotoxicity in submicromolar and low micromolar concentration against both cisplatin (CisPt) sensitive and resistant cells. The results showed a significant effect of the pendant N-heterocycle on the ferrocene derivative toxicity and selectivity against cancer cells. Ultimately, ferrocene derivatives bearing either piperidine or morpholine groups were proposed to be the most promising substitutes for platinum drugs, as they exhibited comparable or even higher activity (in comparison to CisPt) against cancer cells, whereas these compounds were found to exhibit lower toxicity against embryonic HEK293 cells. (C) 2017 Elsevier B.V. All rights reserved.n

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

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

2017

Kód důvěrnosti údajů

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

Název periodika

Journal of Organometallic Chemistry

ISSN

0022-328X

e-ISSN

—

Svazek periodika

846

Číslo periodika v rámci svazku

OCT 2017

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

11

Strana od-do

141-151

Kód UT WoS článku

000407858700018

EID výsledku v databázi Scopus

2-s2.0-85020737791