Interaction of methotrexate, an anticancer agent, with copper(II) ions : coordination pattern, DNA-cleaving properties and cytotoxic studies

2015
journal article
article
20
cris.lastimport.wos2024-04-10T01:11:13Z
dc.abstract.enThe acid–base properties and the Cu(II) binding processes of methotrexate (MTX) were characterized by selected spectroscopic techniques and potentiometric measurements. The pH titration data showed that MTX behaves as a triprotic ligand. The deprotonation constants were determined for α-COOH and γ-COOH groups and (N1)H+ from the pteridine ring. Taking all the obtained results into consideration, a coordination pattern was proposed. The DNA-cleaving activity and reactive oxygen species (ROS) generation were investigated for both MTX and the Cu(II)–MTX system. The complex displayed a promising nuclease activity toward plasmid DNA in the presence of hydrogen peroxide. Interestingly, the induction of ROS, such as hydroxyl radicals, superoxide anions or singlet oxygen, was excluded and a different mechanism of DNA degradation was proposed. As MTX is now commonly used in anticancer therapy i.e. against lung cancer, basic cell-based studies were carried out to establish if its Cu(II) complex exhibits higher cytotoxic properties than the ligand alone. Activities of both compounds were also tested against colon carcinoma. Moreover, the determined values of IC50 were confronted with the cytotoxic activity of cisplatin.pl
dc.affiliationWydział Chemii : Zakład Chemii Nieorganicznejpl
dc.contributor.authorNagaj, Justynapl
dc.contributor.authorKołkowska, Paulinapl
dc.contributor.authorBykowska, Aleksandrapl
dc.contributor.authorKomarnicka, Urszula K.pl
dc.contributor.authorKyzioł, Agnieszka - 147927 pl
dc.contributor.authorJeżowska-Bojczuk, Małgorzatapl
dc.date.accession2019-02-15pl
dc.date.accessioned2015-07-07T09:47:36Z
dc.date.available2015-07-07T09:47:36Z
dc.date.issued2015pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number1pl
dc.description.physical115-123pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume24pl
dc.identifier.doi10.1007/s00044-014-1074-1pl
dc.identifier.eissn1554-8120pl
dc.identifier.issn1054-2523pl
dc.identifier.projectROD UJ / Ppl
dc.identifier.urihttp://ruj.uj.edu.pl/xmlui/handle/item/11915
dc.identifier.weblinkhttps://link.springer.com/content/pdf/10.1007%2Fs00044-014-1074-1.pdfpl
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeinne
dc.subtypeArticlepl
dc.titleInteraction of methotrexate, an anticancer agent, with copper(II) ions : coordination pattern, DNA-cleaving properties and cytotoxic studiespl
dc.title.journalMedicinal Chemistry Researchpl
dc.typeJournalArticlepl
dspace.entity.typePublication
cris.lastimport.wos
2024-04-10T01:11:13Z
dc.abstract.enpl
The acid–base properties and the Cu(II) binding processes of methotrexate (MTX) were characterized by selected spectroscopic techniques and potentiometric measurements. The pH titration data showed that MTX behaves as a triprotic ligand. The deprotonation constants were determined for α-COOH and γ-COOH groups and (N1)H+ from the pteridine ring. Taking all the obtained results into consideration, a coordination pattern was proposed. The DNA-cleaving activity and reactive oxygen species (ROS) generation were investigated for both MTX and the Cu(II)–MTX system. The complex displayed a promising nuclease activity toward plasmid DNA in the presence of hydrogen peroxide. Interestingly, the induction of ROS, such as hydroxyl radicals, superoxide anions or singlet oxygen, was excluded and a different mechanism of DNA degradation was proposed. As MTX is now commonly used in anticancer therapy i.e. against lung cancer, basic cell-based studies were carried out to establish if its Cu(II) complex exhibits higher cytotoxic properties than the ligand alone. Activities of both compounds were also tested against colon carcinoma. Moreover, the determined values of IC50 were confronted with the cytotoxic activity of cisplatin.
dc.affiliationpl
Wydział Chemii : Zakład Chemii Nieorganicznej
dc.contributor.authorpl
Nagaj, Justyna
dc.contributor.authorpl
Kołkowska, Paulina
dc.contributor.authorpl
Bykowska, Aleksandra
dc.contributor.authorpl
Komarnicka, Urszula K.
dc.contributor.authorpl
Kyzioł, Agnieszka - 147927
dc.contributor.authorpl
Jeżowska-Bojczuk, Małgorzata
dc.date.accessionpl
2019-02-15
dc.date.accessioned
2015-07-07T09:47:36Z
dc.date.available
2015-07-07T09:47:36Z
dc.date.issuedpl
2015
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
1
dc.description.physicalpl
115-123
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
24
dc.identifier.doipl
10.1007/s00044-014-1074-1
dc.identifier.eissnpl
1554-8120
dc.identifier.issnpl
1054-2523
dc.identifier.projectpl
ROD UJ / P
dc.identifier.uri
http://ruj.uj.edu.pl/xmlui/handle/item/11915
dc.identifier.weblinkpl
https://link.springer.com/content/pdf/10.1007%2Fs00044-014-1074-1.pdf
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
inne
dc.subtypepl
Article
dc.titlepl
Interaction of methotrexate, an anticancer agent, with copper(II) ions : coordination pattern, DNA-cleaving properties and cytotoxic studies
dc.title.journalpl
Medicinal Chemistry Research
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

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