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Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors
Inhibition of histone deacetylases (HDACs) has been extensively studied in the development of anticancer drugs. In the discovery of potent HDAC inhibitors with novel structures, the 2-substituted phenylquinoline-4-carboxylic acid group was introduced to the cap moiety of HDAC inhibitors. In total, 3...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333195/ https://www.ncbi.nlm.nih.gov/pubmed/35910736 http://dx.doi.org/10.3389/fchem.2022.937225 |
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author | Hui, Qian Zhang, Lihui Feng, Jinhong Zhang, Lei |
author_facet | Hui, Qian Zhang, Lihui Feng, Jinhong Zhang, Lei |
author_sort | Hui, Qian |
collection | PubMed |
description | Inhibition of histone deacetylases (HDACs) has been extensively studied in the development of anticancer drugs. In the discovery of potent HDAC inhibitors with novel structures, the 2-substituted phenylquinoline-4-carboxylic acid group was introduced to the cap moiety of HDAC inhibitors. In total, 30 compounds were synthesized with hydroxamic acid or hydrazide zinc-binding groups. In the enzyme inhibitory test, active compound D28 and its analog D29 exhibited significant HDAC3 selectivity against HDAC1, 2, 3, and 6. However, compared with D28, the hydrazide-bearing compounds (D29 and D30) with remarkably improved enzyme inhibitory activities did not exhibit significant antiproliferative potency in the in vitro anticancer study. Further K562 cell-based mechanistic results revealed that induction of G2/M cell cycle arrest and promotion of apoptosis make important contributions to the anticancer effects of molecule D28. Collectively, an HDAC3 selective inhibitor (D28) with potent in vitro anticancer activity was developed as a lead compound for the treatment of cancer. |
format | Online Article Text |
id | pubmed-9333195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93331952022-07-29 Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors Hui, Qian Zhang, Lihui Feng, Jinhong Zhang, Lei Front Chem Chemistry Inhibition of histone deacetylases (HDACs) has been extensively studied in the development of anticancer drugs. In the discovery of potent HDAC inhibitors with novel structures, the 2-substituted phenylquinoline-4-carboxylic acid group was introduced to the cap moiety of HDAC inhibitors. In total, 30 compounds were synthesized with hydroxamic acid or hydrazide zinc-binding groups. In the enzyme inhibitory test, active compound D28 and its analog D29 exhibited significant HDAC3 selectivity against HDAC1, 2, 3, and 6. However, compared with D28, the hydrazide-bearing compounds (D29 and D30) with remarkably improved enzyme inhibitory activities did not exhibit significant antiproliferative potency in the in vitro anticancer study. Further K562 cell-based mechanistic results revealed that induction of G2/M cell cycle arrest and promotion of apoptosis make important contributions to the anticancer effects of molecule D28. Collectively, an HDAC3 selective inhibitor (D28) with potent in vitro anticancer activity was developed as a lead compound for the treatment of cancer. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9333195/ /pubmed/35910736 http://dx.doi.org/10.3389/fchem.2022.937225 Text en Copyright © 2022 Hui, Zhang, Feng and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Hui, Qian Zhang, Lihui Feng, Jinhong Zhang, Lei Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors |
title | Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors |
title_full | Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors |
title_fullStr | Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors |
title_full_unstemmed | Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors |
title_short | Discovery of 2-Phenylquinoline-4-Carboxylic Acid Derivatives as Novel Histone Deacetylase Inhibitors |
title_sort | discovery of 2-phenylquinoline-4-carboxylic acid derivatives as novel histone deacetylase inhibitors |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333195/ https://www.ncbi.nlm.nih.gov/pubmed/35910736 http://dx.doi.org/10.3389/fchem.2022.937225 |
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