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

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-C...

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Autores principales: Nagaj, Justyna, Kołkowska, Paulina, Bykowska, Aleksandra, Komarnicka, Urszula K., Kyzioł, Agnieszka, Jeżowska-Bojczuk, Małgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284383/
https://www.ncbi.nlm.nih.gov/pubmed/25589824
http://dx.doi.org/10.1007/s00044-014-1074-1
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author Nagaj, Justyna
Kołkowska, Paulina
Bykowska, Aleksandra
Komarnicka, Urszula K.
Kyzioł, Agnieszka
Jeżowska-Bojczuk, Małgorzata
author_facet Nagaj, Justyna
Kołkowska, Paulina
Bykowska, Aleksandra
Komarnicka, Urszula K.
Kyzioł, Agnieszka
Jeżowska-Bojczuk, Małgorzata
author_sort Nagaj, Justyna
collection PubMed
description 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 IC(50) were confronted with the cytotoxic activity of cisplatin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-014-1074-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-42843832015-01-12 Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies Nagaj, Justyna Kołkowska, Paulina Bykowska, Aleksandra Komarnicka, Urszula K. Kyzioł, Agnieszka Jeżowska-Bojczuk, Małgorzata Med Chem Res Original Research 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 IC(50) were confronted with the cytotoxic activity of cisplatin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-014-1074-1) contains supplementary material, which is available to authorized users. Springer US 2014-07-04 2015 /pmc/articles/PMC4284383/ /pubmed/25589824 http://dx.doi.org/10.1007/s00044-014-1074-1 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Research
Nagaj, Justyna
Kołkowska, Paulina
Bykowska, Aleksandra
Komarnicka, Urszula K.
Kyzioł, Agnieszka
Jeżowska-Bojczuk, Małgorzata
Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies
title Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies
title_full Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies
title_fullStr Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies
title_full_unstemmed Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies
title_short Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies
title_sort interaction of methotrexate, an anticancer agent, with copper(ii) ions: coordination pattern, dna-cleaving properties and cytotoxic studies
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284383/
https://www.ncbi.nlm.nih.gov/pubmed/25589824
http://dx.doi.org/10.1007/s00044-014-1074-1
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