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.

Amato J., Miglietta G., Morigi R., Iaccarino N., Locatelli A., Leoni A., et al. (2020). Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells. JOURNAL OF MEDICINAL CHEMISTRY, 63(6), 3090-3103 [10.1021/acs.jmedchem.9b01866].

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

Miglietta G.;Morigi R.
;
Locatelli A.;Leoni A.;Capranico G.
;
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
Amato J., Miglietta G., Morigi R., Iaccarino N., Locatelli A., Leoni A., et al. (2020). Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells. JOURNAL OF MEDICINAL CHEMISTRY, 63(6), 3090-3103 [10.1021/acs.jmedchem.9b01866].
Amato J.; Miglietta G.; Morigi R.; Iaccarino N.; Locatelli A.; Leoni A.; Novellino E.; Pagano B.; Capranico G.; Randazzo A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/785405
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