Copper(II) quinolinonato-7-carboxamido complexes as potent antitumor agents with broad spectra and selective effects
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Copper(II) quinolinonato-7-carboxamido complexes as potent antitumor agents with broad spectra and selective effects
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CA - Inorganic chemistry
OECD FORD branch
—
Result continuities
Project
<a href="/en/project/LO1305" target="_blank" >LO1305: Development of the center of advanced technologies and materials</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
RSC Advances (online)
ISSN
2046-2069
e-ISSN
—
Volume of the periodical
6
Issue of the periodical within the volume
5
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
3899-3909
UT code for WoS article
000369508800060
EID of the result in the Scopus database
—