Journal
MOLECULES
Volume 26, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/molecules26051327
Keywords
proprotein convertase subtilisin; kexin type 9; low-density lipoprotein cholesterol; cardiovascular diseases; moracin compounds; structure activity relationships; HepG2 cell lines
Funding
- Dongguk University
- National Research Foundation of Korea (NRF)
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The study synthesized natural moracin compounds and their derivatives to inhibit PCSK9 expression, with compound 7 showing higher inhibitory activity. These results contribute to a better understanding of the structure-activity relationships of moracin derivatives.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key factor in several cardiovascular diseases, as it is responsible for the elevation of circulating low-density lipoprotein cholesterol (LDL-C) levels in blood plasma by direct interaction with the LDL receptor. The development of orally available drugs to inhibit this PCSK9-LDLR interaction is a highly desirable objective. Here, we report the synthesis of naturally occurring moracin compounds and their derivatives with a 2-arylbenzofuran motif to inhibit PCSK9 expression. In addition, we discuss a short approach involving the three-step synthesis of moracin C and a divergent method to obtain various analogs from one starting material. Among the tested derivatives, compound 7 (97.1%) was identified as a more potent inhibitor of PCSK9 expression in HepG2 cells than berberine (60.9%). These results provide a better understanding of the structure-activity relationships of moracin derivatives for the inhibition of PCSK9 expression in human hepatocytes.
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