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

Abstract

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.

• Authors: Wenya Weng, Ruidian Li, Yanxia Zhang, Xiaofu Pan, Shicui Jiang, Chuchu Sun, Chi Zhang, Xuemian Lu
• Journal: Frontiers in microbiology (Front Microbiol) Vol. 13 Pg. 1033823 ( 2022) ISSN: 1664-302X [Print] Switzerland
• PMID: 36225350 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Weng, Li, Zhang, Pan, Jiang, Sun, Zhang and Lu.