AUTHOR=Weng Wenya , Jiang Shicui , Sun Chuchu , Pan Xiaofu , Xian Li , Lu Xuemian , Zhang Chi 

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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1099592

DOI=10.3389/fmicb.2022.1099592

ISSN=1664-302X

ABSTRACT=Chemical survey on Penicillium sp. YT2019-3321, an endophytic fungus derived from traditional Chinese medicine Lonicera Japonica, resulted in the isolation of eight structurally diversified secondary metabolites, including two previously unreported polyketides, named (±)-chrysoalide B (1) and penicidone E (2). The chemical structures of the isolated compounds were established by a correlative interpretation of HRESIMS and NMR spectroscopic data. The optical resolution of (±)-1 by chiral HPLC yielded individual enantiomers (+)-1 and (−)-1, and their stereochemistry were solved by X-ray diffraction crystallography, respectively. Compound 2 possessed the γ-pyridone nucleus, which is rarely found in natural products. Cytotoxic assay revealed that the new compound 2 significantly induced apoptosis of human pancreatic tumor cells (PATU8988T), 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.