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A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies
“Drug repositioning” is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La(3+), Sm(3+), Eu(3+), Gd(...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412414/ https://www.ncbi.nlm.nih.gov/pubmed/36015158 http://dx.doi.org/10.3390/ph15081010 |
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author | Maciuca, Ana-Madalina Munteanu, Alexandra-Cristina Mihaila, Mirela Badea, Mihaela Olar, Rodica Nitulescu, George Mihai Munteanu, Cristian V. A. Uivarosi, Valentina |
author_facet | Maciuca, Ana-Madalina Munteanu, Alexandra-Cristina Mihaila, Mirela Badea, Mihaela Olar, Rodica Nitulescu, George Mihai Munteanu, Cristian V. A. Uivarosi, Valentina |
author_sort | Maciuca, Ana-Madalina |
collection | PubMed |
description | “Drug repositioning” is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La(3+), Sm(3+), Eu(3+), Gd(3+), Tb(3+)); the experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms, findings that are supported by DFT calculations. The cytotoxic activity of the complexes has been studied using the tumoral cell lines, MDA-MB-231 and LoVo, and a normal cell line, HUVEC. The most active compounds of the series display selective activity against LoVo. Their affinity for DNA and the manner of binding have been tested using UV–Vis spectroscopy and competitive binding studies; our results indicate that major and minor groove binding play a significant role in these interactions. The affinity towards serum proteins has also been evaluated, the complexes displaying higher affinity towards albumin than apotransferrin. |
format | Online Article Text |
id | pubmed-9412414 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94124142022-08-27 A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies Maciuca, Ana-Madalina Munteanu, Alexandra-Cristina Mihaila, Mirela Badea, Mihaela Olar, Rodica Nitulescu, George Mihai Munteanu, Cristian V. A. Uivarosi, Valentina Pharmaceuticals (Basel) Article “Drug repositioning” is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La(3+), Sm(3+), Eu(3+), Gd(3+), Tb(3+)); the experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms, findings that are supported by DFT calculations. The cytotoxic activity of the complexes has been studied using the tumoral cell lines, MDA-MB-231 and LoVo, and a normal cell line, HUVEC. The most active compounds of the series display selective activity against LoVo. Their affinity for DNA and the manner of binding have been tested using UV–Vis spectroscopy and competitive binding studies; our results indicate that major and minor groove binding play a significant role in these interactions. The affinity towards serum proteins has also been evaluated, the complexes displaying higher affinity towards albumin than apotransferrin. MDPI 2022-08-17 /pmc/articles/PMC9412414/ /pubmed/36015158 http://dx.doi.org/10.3390/ph15081010 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maciuca, Ana-Madalina Munteanu, Alexandra-Cristina Mihaila, Mirela Badea, Mihaela Olar, Rodica Nitulescu, George Mihai Munteanu, Cristian V. A. Uivarosi, Valentina A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies |
title | A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies |
title_full | A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies |
title_fullStr | A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies |
title_full_unstemmed | A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies |
title_short | A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies |
title_sort | study on repositioning nalidixic acid via lanthanide complexation: synthesis, characterization, cytotoxicity and dna/protein binding studies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412414/ https://www.ncbi.nlm.nih.gov/pubmed/36015158 http://dx.doi.org/10.3390/ph15081010 |
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