Isoechinulin-Type Diketopiperazines with Anti-monocyte Adhesion Activities from a Sponge-Associated <i>Aspergillus</i> sp

Seven new isoechinulin-type diketopiperazines (DKPs), asperfatsines A-G (<b>1</b>-<b>7</b>), along with five known analogues (<b>8</b>-<b>12</b>), were isolated from cultures of a sponge-associated <i>Aspergillus</i> 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 <b>1</b>, <b>3</b>, <b>4</b>, and <b>8</b> 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 <b>4</b> 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.