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Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90

In the context of our SAR study concerning 6BrCaQ analogues as C-terminal Hsp90 inhibitors, we designed and synthesized a novel series of 3-(heteroaryl)quinolin-2(1H), of types 3, 4, and 5, as a novel class of analogues. A Pd-catalyzed Liebeskind–Srogl cross-coupling was developed as a convenient ap...

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Autores principales: Larghi, Enrique L., Bruneau, Alexandre, Sauvage, Félix, Alami, Mouad, Vergnaud-Gauduchon, Juliette, Messaoudi, Samir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778022/
https://www.ncbi.nlm.nih.gov/pubmed/35056725
http://dx.doi.org/10.3390/molecules27020412
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author Larghi, Enrique L.
Bruneau, Alexandre
Sauvage, Félix
Alami, Mouad
Vergnaud-Gauduchon, Juliette
Messaoudi, Samir
author_facet Larghi, Enrique L.
Bruneau, Alexandre
Sauvage, Félix
Alami, Mouad
Vergnaud-Gauduchon, Juliette
Messaoudi, Samir
author_sort Larghi, Enrique L.
collection PubMed
description In the context of our SAR study concerning 6BrCaQ analogues as C-terminal Hsp90 inhibitors, we designed and synthesized a novel series of 3-(heteroaryl)quinolin-2(1H), of types 3, 4, and 5, as a novel class of analogues. A Pd-catalyzed Liebeskind–Srogl cross-coupling was developed as a convenient approach for easy access to complex purine architectures. This series of analogues showed a promising biological effect against MDA-MB231 and PC-3 cancer cell lines. This study led to the identification of the best compounds, 3b (IC(50) = 28 µM) and 4e, which induce a significant decrease of CDK-1 client protein and stabilize the levels of Hsp90 and Hsp70 without triggering the HSR response.
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spelling pubmed-87780222022-01-22 Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90 Larghi, Enrique L. Bruneau, Alexandre Sauvage, Félix Alami, Mouad Vergnaud-Gauduchon, Juliette Messaoudi, Samir Molecules Communication In the context of our SAR study concerning 6BrCaQ analogues as C-terminal Hsp90 inhibitors, we designed and synthesized a novel series of 3-(heteroaryl)quinolin-2(1H), of types 3, 4, and 5, as a novel class of analogues. A Pd-catalyzed Liebeskind–Srogl cross-coupling was developed as a convenient approach for easy access to complex purine architectures. This series of analogues showed a promising biological effect against MDA-MB231 and PC-3 cancer cell lines. This study led to the identification of the best compounds, 3b (IC(50) = 28 µM) and 4e, which induce a significant decrease of CDK-1 client protein and stabilize the levels of Hsp90 and Hsp70 without triggering the HSR response. MDPI 2022-01-09 /pmc/articles/PMC8778022/ /pubmed/35056725 http://dx.doi.org/10.3390/molecules27020412 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Larghi, Enrique L.
Bruneau, Alexandre
Sauvage, Félix
Alami, Mouad
Vergnaud-Gauduchon, Juliette
Messaoudi, Samir
Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90
title Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90
title_full Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90
title_fullStr Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90
title_full_unstemmed Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90
title_short Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90
title_sort synthesis and biological activity of 3-(heteroaryl)quinolin-2(1h)-ones bis-heterocycles as potential inhibitors of the protein folding machinery hsp90
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778022/
https://www.ncbi.nlm.nih.gov/pubmed/35056725
http://dx.doi.org/10.3390/molecules27020412
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