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.

Autor: Guillon J; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Le Borgne M; Small Molecules for Biological Targets Team, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, CNRS 5286, INSERM 1052, Université Claude Bernard Lyon 1, Univ. Lyon, F-69373 Lyon, France., Milano V; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Guédin-Beaurepaire A; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Moreau S; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Pinaud N; ISM-CNRS UMR 5255, Univ. Bordeaux, F-33405 Talence, France., Ronga L; E2S UPPA, CNRS, IPREM, Université de Pau et des Pays de l'Adour, F-64053 Pau, France., Savrimoutou S; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Albenque-Rubio S; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Marchivie M; ICMCB-UMR 5026, Univ. Bordeaux, F-33608 Pessac, France., Kalout H; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Walker C; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Chevallier L; INSERM, CNRS, ARNA, U1212, UMR 5320, UFR des Sciences Pharmaceutiques, Univ. Bordeaux, F-33076 Bordeaux, France., Buré C; CNRS, INSERM, IECB, US1, UAR 3033, Univ. Bordeaux, F-33600 Pessac, France., Largy E; CNRS, INSERM, ARNA, UMR 5320, U1212, IECB, Univ. Bordeaux, F-33600 Pessac, France., Gabelica V; CNRS, INSERM, ARNA, UMR 5320, U1212, IECB, Univ. Bordeaux, F-33600 Pessac, France., Mergny JL; Ecole Polytechnique, Laboratoire d'Optique et Biosciences, CNRS, INSERM, Institut Polytechnique de Paris, F-91120 Palaiseau, France., Baylot V; Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, CNRS UMR7258, Inserm U1068, Univ. Aix Marseille, F-13009 Marseille, France., Ferrer J; INSERM UMR1312, BRIC, Bordeaux Institute of Oncology, Univ. Bordeaux, F-33076 Bordeaux, France., Idrissi Y; INSERM UMR1312, BRIC, Bordeaux Institute of Oncology, Univ. Bordeaux, F-33076 Bordeaux, France., Chevret E; INSERM UMR1312, BRIC, Bordeaux Institute of Oncology, Univ. Bordeaux, F-33076 Bordeaux, France., Cappellen D; INSERM UMR1312, BRIC, Bordeaux Institute of Oncology, Univ. Bordeaux, F-33076 Bordeaux, France.; Service Tumor Biology and Tumor Bank Laboratory, Groupe Hospitalier Bordeaux, CHU Bordeaux, F-33000 Bordeaux, France., Desplat V; INSERM UMR1312, BRIC, Bordeaux Institute of Oncology, Univ. Bordeaux, F-33076 Bordeaux, France., Schelz Z; Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, 6720 Szeged, Hungary., Zupkó I; Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, 6720 Szeged, Hungary.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Dec 25; Vol. 17 (1). Date of Electronic Publication: 2023 Dec 25.
DOI: 10.3390/ph17010030
Abstrakt: 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-(1 H ,3 H )-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.
Databáze: MEDLINE
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