Molecular networks and bioactivity-guided discovery of aliphatic derivatives from marine-derived fungus Talaromyces sp.

Natural products derived from fungi represent a rich source for the development of new pharmaceuticals. Recent research has demonstrated that numerous secondary metabolites with aliphatic structures exhibit diverse biological activities. Guided by molecular network analysis and assessments of biological activity, three novel compounds (1-3) and one known compound (4) were isolated from marine-derived fungus Talaromyces sp. 6B3. Their structures were elucidated using NMR and HRESIMS data, DP4+ analysis, along with ECD calculations. Compounds 1-4 all possess aliphatic chain structures of varying lengths. The anti-inflammatory activity of the compounds was evaluated in LPS-induced RAW264.7 cells, with all compounds displaying significant anti-inflammatory effects. Notably, compound 1 achieved an inhibition rate of 68.06% on NO release, comparable to that of the positive control dexamethasone. Concurrently, the effects against various pathogenic bacteria were assessed, revealing that compounds 1, 2, and 4 exhibited varying degrees of efficacy against Staphylococcus aureus and Escherichia coli, with MIC ranging from 8 to 32 µg mL-1. This study provides candidate molecules for the development of new drugs derived from natural sources.