Antiglioma Natural Products from the Marine-Associated Fungus Penicillium sp. ZZ1750.
Kuo YongSidra KaleemMingzhu MaXiaoyuan LianZhizhen ZhangPublished in: Molecules (Basel, Switzerland) (2022)
Marine-derived Penicillium fungi are one of the most important sources for the discovery of new bioactive natural products. This study characterized the isolation, structures, and antiglioma activities of twelve compounds, including three novel ones-penipyridinone B ( 1 ), 11 S -(-)-penilloid A ( 2 ), and 11 R ,14 E -(+)-penilloid A ( 3 )-from the marine fungus Penicillium sp. ZZ1750. The structures of the novel compounds were determined via extensive nuclear magnetic resonance (NMR) spectroscopic analyses, high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, Mosher's method, optical rotation (OR) calculations, and electronic circular dichroism (ECD) calculations. Penipyridinone B represents the first example of its structural type and showed potent antiglioma activity, with IC 50 values of 2.45 μM for U87MG cells and 11.40 μM for U251 cells. The known compounds of questiomycin A ( 9 ) and xanthocillin X ( 10 ) also showed antiproliferative activity against both U87MG and U251 cells, with IC 50 values of 13.65 μM to 22.56 μM. The antiglioma activity of questiomycin A and xanthocillin X may be related to the promotion of reactive oxygen species (ROS) production, the reduction of mitochondrial membrane potential (MMP), and the enhancement of caspase-3 enzyme activity.
Keyphrases
- high resolution
- induced apoptosis
- magnetic resonance
- cell cycle arrest
- reactive oxygen species
- cell death
- endoplasmic reticulum stress
- oxidative stress
- signaling pathway
- molecular dynamics simulations
- mass spectrometry
- density functional theory
- electronic health record
- computed tomography
- risk assessment
- molecular docking
- magnetic resonance imaging
- drug induced
- liquid chromatography
- tandem mass spectrometry