Synthesis of Moracin C and Its Derivatives with a 2-arylbenzofuran Motif and Evaluation of Their PCSK9 Inhibitory Effects in HepG2 Cells.

ABSTRACT: 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 PC

SUBMITTER: Masagalli JN 

PROVIDER: S-EPMC7958322 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature