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Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription
Apolipoprotein A-I (Apo A-I) is the principal protein component of high density lipoprotein (HDL), which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268513/ https://www.ncbi.nlm.nih.gov/pubmed/22699570 http://dx.doi.org/10.3390/molecules17067379 |
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author | Du, Yu Yang, Yuan Jiang, Wei Wang, Li Jia, Xiao-Jian Si, Shu-Yi Chen, Xiao-Fang Hong, Bin |
author_facet | Du, Yu Yang, Yuan Jiang, Wei Wang, Li Jia, Xiao-Jian Si, Shu-Yi Chen, Xiao-Fang Hong, Bin |
author_sort | Du, Yu |
collection | PubMed |
description | Apolipoprotein A-I (Apo A-I) is the principal protein component of high density lipoprotein (HDL), which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR) around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future. |
format | Online Article Text |
id | pubmed-6268513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62685132018-12-12 Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription Du, Yu Yang, Yuan Jiang, Wei Wang, Li Jia, Xiao-Jian Si, Shu-Yi Chen, Xiao-Fang Hong, Bin Molecules Communication Apolipoprotein A-I (Apo A-I) is the principal protein component of high density lipoprotein (HDL), which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR) around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future. MDPI 2012-06-14 /pmc/articles/PMC6268513/ /pubmed/22699570 http://dx.doi.org/10.3390/molecules17067379 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Communication Du, Yu Yang, Yuan Jiang, Wei Wang, Li Jia, Xiao-Jian Si, Shu-Yi Chen, Xiao-Fang Hong, Bin Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription |
title | Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription |
title_full | Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription |
title_fullStr | Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription |
title_full_unstemmed | Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription |
title_short | Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription |
title_sort | substituted benzamides containing azaspiro rings as upregulators of apolipoprotein a-i transcription |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268513/ https://www.ncbi.nlm.nih.gov/pubmed/22699570 http://dx.doi.org/10.3390/molecules17067379 |
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