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

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 expression.

Pharmacokinetic Properties of Moracin C in Mice.

Moracin C from fruits, also known as the mulberry, has been proven to exhibit inhibitory activities against lipoxygenase enzymes, TNF- and interleukin-1 secretion, and proprotein convertase subtilisin/kexin type 9 expression. Despite the various pharmacological activities of moracin C, its pharmacokinetic characteristics have yet to be reported. Here, the pharmacokinetic parameters and tissue distribution of moracin C have been investigated in mice, and the plasma concentration of moracin C with multiple dosage regimens was simulated via pharmacokinetic modeling.