Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

• Published in: Marine life science & technology 2024-02, Vol.6 (1), p.84-92
• Main Authors: Jung, Yuna, Kwon, Chaesun, Kim, Taeyeon, Lee, Jin Woo, Shin, Min-Kyoo, Shim, Sang Hee
• Format: Article
• Language: English
• Subjects: Biodiversity; Biological Techniques; Biomedical and Life Sciences; Fish & Wildlife Biology & Management; Food Microbiology; Freshwater & Marine Ecology; Life Sciences; Research Paper
• ISSN: 2662-1746; 2096-6490; 2662-1746
• DOI: 10.1007/s42995-023-00198-7

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological activities. In the present study, two new tetramic acid alkaloids tolypyridone I ( 1 ) and tolypyridone J ( 2 ), together with five known ones ( 3 – 7 ), were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North Alaska. Their structures were elucidated using 1D, 2D NMR, and HRESIMS. Their configurations were established on the basis of 1 H coupling constants, ROESY correlations and DP4 calculations. Compound 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane, hindering rotation. In our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease (PD) model, SH-SY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium (MPP + ), a parkinsonian neurotoxin. Among tested compounds, F-14329 ( 7 ) significantly protected cells from MPP + -induced cytotoxicity. MPP + -mediated cell death is known to be related to the regulation of Bcl-2 family proteins, specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax levels. Treatment with 2 mmol/L of MPP + for 24 h significantly reduced Bcl-2 levels compared to control treated with vehicle. However, treatment with F-14329 ( 7 ) attenuated such reduction. This study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.