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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8778022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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