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Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells
[Image: see text] Targeting G-quadruplex structures is currently viewed as a promising anticancer strategy. Searching for potent and selective G-quadruplex binders, here we describe a small series of new monohydrazone derivatives designed as analogues of a lead which was proved to stabilize G-quadru...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical
Society
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997572/ https://www.ncbi.nlm.nih.gov/pubmed/32142285 http://dx.doi.org/10.1021/acs.jmedchem.9b01866 |
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author | Amato, Jussara Miglietta, Giulia Morigi, Rita Iaccarino, Nunzia Locatelli, Alessandra Leoni, Alberto Novellino, Ettore Pagano, Bruno Capranico, Giovanni Randazzo, Antonio |
author_facet | Amato, Jussara Miglietta, Giulia Morigi, Rita Iaccarino, Nunzia Locatelli, Alessandra Leoni, Alberto Novellino, Ettore Pagano, Bruno Capranico, Giovanni Randazzo, Antonio |
author_sort | Amato, Jussara |
collection | PubMed |
description | [Image: see text] Targeting G-quadruplex structures is currently viewed as a promising anticancer strategy. Searching for potent and selective G-quadruplex binders, here we describe a small series of new monohydrazone derivatives designed as analogues of a lead which was proved to stabilize G-quadruplex structures and increase R loop levels in human cancer cells. To investigate the G-quadruplex binding properties of the new molecules, in vitro biophysical studies were performed employing both telomeric and oncogene promoter G-quadruplex-forming sequences. The obtained results allowed the identification of a highly selective G-quadruplex ligand that, when studied in human cancer cells, proved to be able to stabilize both G-quadruplexes and R loops and showed a potent cell killing activity associated with the formation of micronuclei, a clear sign of genome instability. |
format | Online Article Text |
id | pubmed-7997572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American
Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-79975722021-03-29 Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells Amato, Jussara Miglietta, Giulia Morigi, Rita Iaccarino, Nunzia Locatelli, Alessandra Leoni, Alberto Novellino, Ettore Pagano, Bruno Capranico, Giovanni Randazzo, Antonio J Med Chem [Image: see text] Targeting G-quadruplex structures is currently viewed as a promising anticancer strategy. Searching for potent and selective G-quadruplex binders, here we describe a small series of new monohydrazone derivatives designed as analogues of a lead which was proved to stabilize G-quadruplex structures and increase R loop levels in human cancer cells. To investigate the G-quadruplex binding properties of the new molecules, in vitro biophysical studies were performed employing both telomeric and oncogene promoter G-quadruplex-forming sequences. The obtained results allowed the identification of a highly selective G-quadruplex ligand that, when studied in human cancer cells, proved to be able to stabilize both G-quadruplexes and R loops and showed a potent cell killing activity associated with the formation of micronuclei, a clear sign of genome instability. American Chemical Society 2020-03-06 2020-03-26 /pmc/articles/PMC7997572/ /pubmed/32142285 http://dx.doi.org/10.1021/acs.jmedchem.9b01866 Text en Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Amato, Jussara Miglietta, Giulia Morigi, Rita Iaccarino, Nunzia Locatelli, Alessandra Leoni, Alberto Novellino, Ettore Pagano, Bruno Capranico, Giovanni Randazzo, Antonio Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells |
title | Monohydrazone Based
G-Quadruplex Selective
Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells |
title_full | Monohydrazone Based
G-Quadruplex Selective
Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells |
title_fullStr | Monohydrazone Based
G-Quadruplex Selective
Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells |
title_full_unstemmed | Monohydrazone Based
G-Quadruplex Selective
Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells |
title_short | Monohydrazone Based
G-Quadruplex Selective
Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells |
title_sort | monohydrazone based
g-quadruplex selective
ligands induce dna damage and genome instability in human cancer cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997572/ https://www.ncbi.nlm.nih.gov/pubmed/32142285 http://dx.doi.org/10.1021/acs.jmedchem.9b01866 |
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