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.

Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells / Amato, J.; Miglietta, G.; Morigi, R.; Iaccarino, N.; Locatelli, A.; Leoni, A.; Novellino, E.; Pagano, B.; Capranico, G.; Randazzo, A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - 63:6(2020), pp. 3090-3103. [10.1021/acs.jmedchem.9b01866]

Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells

Amato J.
Co-primo
;
Iaccarino N.;Novellino E.;Pagano B.;Randazzo A.
Co-ultimo
2020

Abstract

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.
2020
Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells / Amato, J.; Miglietta, G.; Morigi, R.; Iaccarino, N.; Locatelli, A.; Leoni, A.; Novellino, E.; Pagano, B.; Capranico, G.; Randazzo, A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - 63:6(2020), pp. 3090-3103. [10.1021/acs.jmedchem.9b01866]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/801475
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