Copper(II) quinolinonato-7-carboxamido complexes as potent antitumor agents with broad spectra and selective effects

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33161189" target="_blank" >RIV/61989592:15310/16:33161189 - isvavai.cz</a>

Výsledek na webu

<a href="http://pubs.rsc.org/en/content/articlepdf/2016/ra/c5ra22141b" target="_blank" >http://pubs.rsc.org/en/content/articlepdf/2016/ra/c5ra22141b</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c5ra22141b" target="_blank" >10.1039/c5ra22141b</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Copper(II) quinolinonato-7-carboxamido complexes as potent antitumor agents with broad spectra and selective effects

Popis výsledku v původním jazyce

A series of five copper(II) mixed-ligand complexes with the composition [Cu(qui(x))(phen)]NO3 center dot yH(2)O (1 to 5), where Hqui(x) stands for 2-(4-amino-3,5-dichlorophenyl)-3-hydroxy-4(1H)-quinolinone-7-carboxamides with different N-substitutions: Hqui(1) = N-propyl (1), Hqui(2) = N-isobutyl (2), Hqui(3) = N-cyclohexyl (3), Hqui(4) = N-benzyl (4), and Hqui(5) = N-p-xylyl (5); phen = 1,10-phenanthroline and y = 0 or 1, were synthesized, characterized and screened for in vitro antitumor activity on a panel of six human cancer cell lines, including osteosarcoma (HOS), breast adenocarcinoma (MCF7), malignant melanoma (G361), cervix carcinoma (HeLa), ovarian carcinoma (A2780) and cisplatin-resistant ovarian carcinoma (A2780R). All the complexes, except for limitedly soluble complex 4, showed very potent cytotoxicity (IC50 approximate to 1-7 mu M); the best IC50 value was found for complex 5 against A2780, with IC50 = 0.6(1) mu M. Moreover, complex 5 was found to be non-toxic up to 50 mu M against non-malignant lung fibroblast cells (MRC-5); therefore, showing a promising selectivity index [IC50(MRC-5)/IC50(A2780)] that was higher than 80. The complexes were also shown to bind to calf thymus DNA, interact with physiological levels of L-cysteine and act as chemical nucleases. It was additionally suggested that the species responsible for the biological activities of the prepared complexes were the [Cu(qui)(phen)](+) cations, or similar cationic species containing the {Cu(phen)} residue. The results clearly demonstrated that targeted structural optimization of the quinolinonato ligand in this class of complexes leads to compounds with high-level and broad-spectrum anticancer activity along with significantly increased selectivity.

Název v anglickém jazyce

Copper(II) quinolinonato-7-carboxamido complexes as potent antitumor agents with broad spectra and selective effects

Popis výsledku anglicky

A series of five copper(II) mixed-ligand complexes with the composition [Cu(qui(x))(phen)]NO3 center dot yH(2)O (1 to 5), where Hqui(x) stands for 2-(4-amino-3,5-dichlorophenyl)-3-hydroxy-4(1H)-quinolinone-7-carboxamides with different N-substitutions: Hqui(1) = N-propyl (1), Hqui(2) = N-isobutyl (2), Hqui(3) = N-cyclohexyl (3), Hqui(4) = N-benzyl (4), and Hqui(5) = N-p-xylyl (5); phen = 1,10-phenanthroline and y = 0 or 1, were synthesized, characterized and screened for in vitro antitumor activity on a panel of six human cancer cell lines, including osteosarcoma (HOS), breast adenocarcinoma (MCF7), malignant melanoma (G361), cervix carcinoma (HeLa), ovarian carcinoma (A2780) and cisplatin-resistant ovarian carcinoma (A2780R). All the complexes, except for limitedly soluble complex 4, showed very potent cytotoxicity (IC50 approximate to 1-7 mu M); the best IC50 value was found for complex 5 against A2780, with IC50 = 0.6(1) mu M. Moreover, complex 5 was found to be non-toxic up to 50 mu M against non-malignant lung fibroblast cells (MRC-5); therefore, showing a promising selectivity index [IC50(MRC-5)/IC50(A2780)] that was higher than 80. The complexes were also shown to bind to calf thymus DNA, interact with physiological levels of L-cysteine and act as chemical nucleases. It was additionally suggested that the species responsible for the biological activities of the prepared complexes were the [Cu(qui)(phen)](+) cations, or similar cationic species containing the {Cu(phen)} residue. The results clearly demonstrated that targeted structural optimization of the quinolinonato ligand in this class of complexes leads to compounds with high-level and broad-spectrum anticancer activity along with significantly increased selectivity.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CA - Anorganická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/LO1305" target="_blank" >LO1305: Rozvoj centra pokročilých technologií a materiálů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

RSC Advances (online)

ISSN

2046-2069

e-ISSN

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Svazek periodika

6

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

3899-3909

Kód UT WoS článku

000369508800060

EID výsledku v databázi Scopus

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