A Novel Bis-Spiroketal Scaffold and Other Secondary Metabolites from the Marine-Derived Fungus Talaromyces stipitatus HF05001: Structural Diversity and Bioactivities

Marine-derived fungi have become a vital resource for the discovery of novel secondary metabolites with diverse structures and significant biological activities. This study focuses on a systematic chemical investigation of the sponge-associated fungus <i>Talaromyces stipitatus</i> HF05001, leading to the isolation and identification of 20 compounds, including one new marine ketal natural product (Compound <b>17</b>, Talarobispiral A). These compounds were structurally elucidated using comprehensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS. All isolates were screened for their anti-inflammatory and anti-adipogenic properties. Among them, compound <b>4</b> (Secalonic acid D, SAD), <b>7</b> (Sch 725680) and <b>16</b> (bacillisporins C) demonstrated significant anti-inflammatory potential by markedly suppressing nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Notably, compound <b>4</b> showed superior inhibitory effect, with an IC₅₀ value of 0.22 μM. Additionally, compound <b>4</b> exhibited the strongest dose-dependent inhibition of lipid droplet accumulation in 3T3-L1 preadipocytes. These findings highlight the dual therapeutic potential of metabolites from <i>Talaromyces stipitatus</i>, identifying promising lead compounds for the development of novel treatments for inflammatory and metabolic disorders.