Versicotides D–F, new cyclopeptides with lipid-lowering activities

Abstract

Lipid-lowering assay guided fractionation of a gorgonian-derived fungus Aspergillus versicolor LZD-14-1 resulted in the isolation of three new cyclopeptides namely versicotides D–F (1–3) and the known analogues versicotides A and B. The new structures were determined by extensive spectroscopic data (1D and 2D NMR, HRESIMS), while the data of the X-ray crystallography and Marfey's method were used for the configurational assignment. Versicotides E–F (2–3) are characterized by the presence of two anthranilic acid residues and a proline that coexisted in the cyclic pentapeptides, which are rarely found from nature. Versicotides D–F (1–3) exerted lipid-lowering effects through the regulation of cholesterol efflux to HDL in RAW264.7 macrophages. The mechanistic study revealed that the cholesterol efflux and influx induced by the peptides are directly related to the promotion of the target genes ABCG1 and LXRα, in addition to the decreasing critical scavenger receptors CD36 and SR-1/SR-2. The present work provided a group of new cyclopeptides which are promising for the development of anti-atherosclerosis leads.