Design and synthesis of novel chlorogenic acid analogues targeting ACAT1.

Abstract

Twenty chlorogenic acid analogues had been designed and synthesized targeting mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1). The structures of these analogues were confirmed by MS and NMR. In addition, computer-aided drug design technology was used to perform molecular docking with key amino acid residues and identify the active groups binding to the active sites. In vitro activity assays showed that compounds 3b and 5d exhibited 10-fold higher ACAT1 inhibitory activity than chlorogenic acid. Compounds 3a, 3 l, 3p, 4f, 4 g, 5a and 5q exhibited ACAT1 inhibitory activity comparable to that of chlorogenic acid. These findings contribute to the preliminary elucidation of the structure-activity relationship (SAR) of chlorogenic acid analogues targeting ACAT1.

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