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

TITLE=Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1033823

DOI=10.3389/fmicb.2022.1033823

ISSN=1664-302X

ABSTRACT=<p>Fungal secondary metabolites are inherently considered valuable resources for new drugs discovery. To search for novel fungal secondary metabolites with lead compounds potential, a fungal strain <italic>Penicillium oxalicum</italic> 2021CDF-3, an endophyte of the marine red algae <italic>Rhodomela confervoides</italic>, was chemically studied. Cultivation of this fungus on solid rice medium yielded 10 structurally diverse metabolites (<bold>1</bold>–<bold>10</bold>), including two new polyketides, namely oxalichroman A (<bold>1</bold>) and oxalihexane A (<bold>2</bold>). Their structures were determined by detailed analysis of NMR and HRESIMS spectroscopic data. Oxalihexane A (<bold>2</bold>) was elucidated as a novel polyketide formed by a cyclohexane and cyclohexanone moiety <italic>via</italic> an ether bond. The stereochemistry of <bold>2</bold> was successfully assigned by NMR and ECD calculations. In the cytotoxic assay, the new compound <bold>2</bold> showed remarkable inhibitory effect on the human pancreatic cancer PATU8988T cell line. Further pharmacological study demonstrated that the expression level of Cyclin D1 was down-regulated by the treatment with <bold>2</bold>, which suggested that cell cyclin abnormity was involved in pancreatic tumor cell apoptosis. Moreover, the activation of Wnt5a/Cyclin D1 signaling pathway might be involved in the mechanism of panreatic tumor cell apoptosis induced by <bold>2</bold>.</p>