Bioactive chemical constituents from the marine-derived fungus Cladosporium sp. DLT-5

A new isochromanone, cladosporinisochromanone (1), accompanied by 15 known compounds (2–16) were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp. DLT-5. NMR and HRESIMS spectra elucidation determined the planar structure of 1. Subsequent electronic circular dichroism (ECD) experiment assigned the absolute configuration of 1. Compounds 1, 2, 4–6, and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y. Five compounds (1, 3–5, and 13) emerged resistance to protein tyrosine phosphatase 1B (PTP1B), further kinetic analysis and molecular docking study indicated that the most potent compound 13 (IC₅₀ value of 10.74±0.61 µmol/L) was found as a noncompetitive inhibitor for PTP1B. Surface plasmon resonance (SPR) and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1 (NPC1L1), which has been identified as significant therapeutic target for hypercholesteremia. In addition, compounds 3, 6, and 14 showed attractive inhibitory activity against the phytopathogenic fungi: Colletotrichum capsici. Therefore, library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.