Isoechinulin-Type Diketopiperazines with Anti-monocyte Adhesion Activities from a Sponge-Associated Aspergillus sp

Seven new isoechinulin-type diketopiperazines (DKPs), asperfatsines A-G (1-7), along with five known analogues (8-12), were isolated from cultures of a sponge-associated Aspergillus sp. SCSIO41034. The structural elucidations, including the determination of absolute configurations, were accomplished by comprehensive analyses utilizing NMR spectroscopy, HRESIMS, gas chromatography-mass spectrometry (GC-MS), Marfey's method, Mo2(OAc)4-induced circular dichroism, modified Mosher's method, and electronic circular dichroism (ECD) calculations. Asperfatsines A-C represent the first three cases of isoechinulin-type DKPs possessing three distinct long-chain fatty acid moieties. Pretreatment with 1, 3, 4, and 8 in tumor necrosis factor α (TNF-α)-stimulated human umbilical vein endothelial cells led to a reduction in the adhesion of THP-1 monocytes. Compound 4 downregulates the gene expression of cell adhesion molecules in a dose-dependent manner. These findings suggest that isoechinulin-type DKPs represent promising candidates with core molecular frameworks that may serve as a foundation for developing antivascular inflammation therapies.