Cytotoxic secondary metabolites isolated from Penicillium sp. YT2019-3321, an endophytic fungus derived from Lonicera Japonica

• Published in: Frontiers in microbiology 2022-12, Vol.13, p.1099592-1099592
• Main Authors: Weng, Wenya, Jiang, Shicui, Sun, Chuchu, Pan, Xiaofu, Xian, Li, Lu, Xuemian, Zhang, Chi
• Format: Article
• Language: English
• Subjects: cytotoxic activity; endophytic fungus; Microbiology; Penicillium; polyketides; secondary metabolites
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2022.1099592

Endophytic fungi associated with medicinal plants have proven to possess a high potential to produce structurally diverse metabolites, some of which are valuable for medicinal applications. In this study, sp. YT2019-3321, an endophytic fungus derived from traditional Chinese medicine Lonicera japonica, was chemically studied. The chemical structures of the isolated compounds were established by a correlative interpretation of HRESIMS and NMR spectroscopic data. The optical resolution of (±)- by chiral HPLC yielded individual enantiomers (+) and (-) , and their stereochemistry were solved by X-ray diffraction crystallography, respectively. Eight structurally diversified secondary metabolites, including two previously unreported polyketides, named (±)-chrysoalide B ( ) and penicidone E ( ), were isolated and identified from Penicillium sp. YT2019-3321. Compound 2 possessed the γ-pyridone nucleus, which is rarely found in natural products. Cytotoxic assay revealed that the new compound 2 demonstrated a dose-dependent cytotoxicity against the human pancreatic tumor cells PATU8988T with the IC value of 11.4 μM. Further studies indicated that significantly induced apoptosis of PATU8988T cell lines, characterized by the morphologies abnormity, the reduction of cell number, the upregulation of proportion of apoptotic cells, and the ratio of Bcl-2 to Bax. Our study demonstrates that fungal secondary metabolites may have important significance in the discovery of drug leads.