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

• Published in: Frontiers in microbiology 2022-09, Vol.13, p.1033823-1033823
• Main Authors: Weng, Wenya, Li, Ruidian, Zhang, Yanxia, Pan, Xiaofu, Jiang, Shicui, Sun, Chuchu, Zhang, Chi, Lu, Xuemian
• Format: Article
• Language: English
• Subjects: algal-derived fungus; cytotoxic activity; Microbiology; Penicillium oxalicum; polyketides; secondary metabolites
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2022.1033823

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 Penicillium oxalicum 2021CDF-3, an endophyte of the marine red algae Rhodomela confervoides , was chemically studied. Cultivation of this fungus on solid rice medium yielded 10 structurally diverse metabolites ( 1 – 10 ), including two new polyketides, namely oxalichroman A ( 1 ) and oxalihexane A ( 2 ). Their structures were determined by detailed analysis of NMR and HRESIMS spectroscopic data. Oxalihexane A ( 2 ) was elucidated as a novel polyketide formed by a cyclohexane and cyclohexanone moiety via an ether bond. The stereochemistry of 2 was successfully assigned by NMR and ECD calculations. In the cytotoxic assay, the new compound 2 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 2 , 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 2 .