In vitro and In silico Inhibitory Investigations of elastase release in fMLF/CB-Induced human neutrophils of ısolated naphtopyrones from marine fungi Aspergillus Niger

In this study, the secondary metabolites produced by Aspergillus niger associated with the tunicate Microcosmus vulgaris collected from the Aegean Sea (Turkiye) were explored. Five known naphtopyrones, rubrofusarin B (1), flavasperone (2), aurasperone B (3), fonsecinone D (4), aurasperone A (7), and two known disaccharides, α,α-trehalose (5) and β,β-trehalose (6) were isolated. Compounds were elucidated using 1D and 2D NMR spectroscopy and by comparing coupling constants and optical rotation values with literature data. Compounds (1–4) were evaluated for the first time in vitro anti-inflammatory activity via human neutrophil elastase (HNE) release induced by fMLF/CB. The most potent compound was aurasperone B (10 µM) with 20.33% inhibition, following fonsecinone D (10 µM) with 11.83% inhibition, compared to the standard genistein (3 µM) with 31.57% inhibition. Molecular docking of compounds (1–4 and 7) against HNE (PDB ID: 1H1B) indicated efficient enzyme inhibition by interactions with key residues of the active site. Aurasperone B (3), which exhibits the second highest binding affinity, and fonsecinone D (4) are discovered potential candidates for further biological and pharmacological studies to validate their therapeutic potential.