Abstract: 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.
Keywords: apolipoprotein A-I; transcriptional upregulator; structure-activity relationship; atherosclerosis
Export to BibTeX
MDPI and ACS Style
Du, Y.; Yang, Y.; Jiang, W.; Wang, L.; Jia, X.-J.; Si, S.-Y.; Chen, X.-F.; Hong, B. Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription. Molecules 2012, 17, 7379-7386.
Du Y, Yang Y, Jiang W, Wang L, Jia X-J, Si S-Y, Chen X-F, Hong B. Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription. Molecules. 2012; 17(6):7379-7386.
Du, Yu; Yang, Yuan; Jiang, Wei; Wang, Li; Jia, Xiao-Jian; Si, Shu-Yi; Chen, Xiao-Fang; Hong, Bin. 2012. "Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription." Molecules 17, no. 6: 7379-7386.