A New Natural Indole Diketopiperazine Alkaloid from Marine-derived Penicillium chrysogenum BTBU20212052

Background: Marine-derived fungi have shown great potential for discovering new bioactive secondary metabolites. Method: The fungus strain Penicillium chrysogenum BTBU20212025 was fermented at 28°C for 30 days under static conditions using a rice medium. Then, the extract of the fermented materials was subjected to chromatography to yield compounds 1-9. The chemical structures of the isolated compounds were determined by comprehensive analysis of 1D and 2D NMR and high-resolution mass spectrometry. Additionally, the antibacterial activity was performed in a 96-well plate format using the microdilution method in an MHB broth medium. Result: A new natural diketopiperazine derivative, 12-hydroxy-cyclo-(L-tryptophyl-L-phenylalanyl) (1), along with eight known compounds, including cyclo-(L-tryptophyl-L-phenylalanyl) (2), haenamindole (3), meleagrin (4), citreohybridonol (5), 1,3,6-trihydroxy-7-(1',2'-dihydroxypropan-2-yl)- anthraquinone (6), citreoisocoumarinol (7), penicillocitrin A (8), and methyl 2-(2,6- dihydroxybenzoyl)-3-hydroxy-5-(hydroxymethyl)benzoate (9), was identified from Penicillium chrysogenum BTBU20212025. Compounds 4, 6, and 8 exhibited inhibitory effects against Staphylococcus aureus with a minimum inhibitory concentration value of 50 μg/mL. method: Optical rotations were measured by an Anton Paar MCP 200 Modular Circular polarimeter. NMR spectra were reordered on a Bruker Avance 500 MHz spectrometer at 25 °C with solvent residue as references. HRESIMS was measured by using Waters G2-XS QTOF mass spectrometer. Column chromatography was performed on normal phase silica gel (thin layer chromatography H silica) and Sephadex LH-20. Semi-preparative high performance liquid chromatography (HPLC) was performed on an Agilent 1260 instrument with a diode array detector by using Agilent Eclipse XDB-C8 column (250 × 9.4 mm, 5 um) at 28 °C. Conclusion: The marine-derived fungus strain Penicillium chrysogenum BTBU20212025 showed potential for producing new and antibacterial natural products.