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Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA
Guanine-rich DNA can form four-stranded structures called G-quadruplexes (G4s) that can regulate many biological processes. Metal complexes have shown high affinity and selectivity toward the quadruplex structure. Here, we report the comparison of a panel of platinum (II) complexes for quadruplex DN...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385020/ https://www.ncbi.nlm.nih.gov/pubmed/30678027 http://dx.doi.org/10.3390/molecules24030404 |
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author | Morel, Elodie Beauvineau, Claire Naud-Martin, Delphine Landras-Guetta, Corinne Verga, Daniela Ghosh, Deepanjan Achelle, Sylvain Mahuteau-Betzer, Florence Bombard, Sophie Teulade-Fichou, Marie-Paule |
author_facet | Morel, Elodie Beauvineau, Claire Naud-Martin, Delphine Landras-Guetta, Corinne Verga, Daniela Ghosh, Deepanjan Achelle, Sylvain Mahuteau-Betzer, Florence Bombard, Sophie Teulade-Fichou, Marie-Paule |
author_sort | Morel, Elodie |
collection | PubMed |
description | Guanine-rich DNA can form four-stranded structures called G-quadruplexes (G4s) that can regulate many biological processes. Metal complexes have shown high affinity and selectivity toward the quadruplex structure. Here, we report the comparison of a panel of platinum (II) complexes for quadruplex DNA selective recognition by exploring the aromatic core around terpyridine derivatives. Their affinity and selectivity towards G4 structures of various topologies have been evaluated by FRET-melting (Fluorescence Resonance Energy Transfert-melting) and Fluorescent Intercalator Displacement (FID) assays, the latter performed by using three different fluorescent probes (Thiazole Orange (TO), TO-PRO-3, and PhenDV). Their ability to bind covalently to the c-myc G4 structure in vitro and their cytotoxicity potential in two ovarian cancerous cell lines were established. Our results show that the aromatic surface of the metallic ligands governs, in vitro, their affinity, their selectivity for the G4 over the duplex structures, and platination efficiency. However, the structural modifications do not allow significant discrimination among the different G4 topologies. Moreover, all compounds were tested on ovarian cancer cell lines and normal cell lines and were all able to overcome cisplatin resistance highlighting their interest as new anticancer drugs. |
format | Online Article Text |
id | pubmed-6385020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63850202019-02-23 Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA Morel, Elodie Beauvineau, Claire Naud-Martin, Delphine Landras-Guetta, Corinne Verga, Daniela Ghosh, Deepanjan Achelle, Sylvain Mahuteau-Betzer, Florence Bombard, Sophie Teulade-Fichou, Marie-Paule Molecules Article Guanine-rich DNA can form four-stranded structures called G-quadruplexes (G4s) that can regulate many biological processes. Metal complexes have shown high affinity and selectivity toward the quadruplex structure. Here, we report the comparison of a panel of platinum (II) complexes for quadruplex DNA selective recognition by exploring the aromatic core around terpyridine derivatives. Their affinity and selectivity towards G4 structures of various topologies have been evaluated by FRET-melting (Fluorescence Resonance Energy Transfert-melting) and Fluorescent Intercalator Displacement (FID) assays, the latter performed by using three different fluorescent probes (Thiazole Orange (TO), TO-PRO-3, and PhenDV). Their ability to bind covalently to the c-myc G4 structure in vitro and their cytotoxicity potential in two ovarian cancerous cell lines were established. Our results show that the aromatic surface of the metallic ligands governs, in vitro, their affinity, their selectivity for the G4 over the duplex structures, and platination efficiency. However, the structural modifications do not allow significant discrimination among the different G4 topologies. Moreover, all compounds were tested on ovarian cancer cell lines and normal cell lines and were all able to overcome cisplatin resistance highlighting their interest as new anticancer drugs. MDPI 2019-01-23 /pmc/articles/PMC6385020/ /pubmed/30678027 http://dx.doi.org/10.3390/molecules24030404 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Morel, Elodie Beauvineau, Claire Naud-Martin, Delphine Landras-Guetta, Corinne Verga, Daniela Ghosh, Deepanjan Achelle, Sylvain Mahuteau-Betzer, Florence Bombard, Sophie Teulade-Fichou, Marie-Paule Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA |
title | Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA |
title_full | Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA |
title_fullStr | Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA |
title_full_unstemmed | Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA |
title_short | Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA |
title_sort | selectivity of terpyridine platinum anticancer drugs for g-quadruplex dna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385020/ https://www.ncbi.nlm.nih.gov/pubmed/30678027 http://dx.doi.org/10.3390/molecules24030404 |
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