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New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline Derivatives: Synthesis and Biological Evaluation as Novel Anticancer Agents by Targeting G-Quadruplex.

Authors :
Guillon, Jean
Le Borgne, Marc
Milano, Vittoria
Guédin-Beaurepaire, Aurore
Moreau, Stéphane
Pinaud, Noël
Ronga, Luisa
Savrimoutou, Solène
Albenque-Rubio, Sandra
Marchivie, Mathieu
Kalout, Haouraa
Walker, Charley
Chevallier, Louise
Buré, Corinne
Largy, Eric
Gabelica, Valérie
Mergny, Jean-Louis
Baylot, Virginie
Ferrer, Jacky
Idrissi, Yamina
Source :
Pharmaceuticals (14248247); Jan2024, Vol. 17 Issue 1, p30, 29p
Publication Year :
2024

Abstract

The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1H,3H)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b, 12f, and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14248247
Volume :
17
Issue :
1
Database :
Complementary Index
Journal :
Pharmaceuticals (14248247)
Publication Type :
Academic Journal
Accession number :
175078969
Full Text :
https://doi.org/10.3390/ph17010030