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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...

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Autores principales: Du, Yu, Yang, Yuan, Jiang, Wei, Wang, Li, Jia, Xiao-Jian, Si, Shu-Yi, Chen, Xiao-Fang, Hong, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
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.
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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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