Anti-Inflammatory Azaphilones from the Edible Alga-Derived Fungus Penicillium sclerotiorum

Abstract

To discover the new medical entity from edible marine algae, our continuously natural product investigation focused on endophytes from marine macroalgae Grateloupia sp. Two new azaphilones, 8a-epi-hypocrellone A (1), 8a-epi-eupenicilazaphilone C (2), together with five known azaphilones, hypocrellone A (3), eupenicilazaphilone C (4), ((1E,3E)-3,5-dimethylhepta-1,3-dien-1-yl)-2,4-dihydroxy-3-methylbenzaldehyde (5), sclerotiorin (6), and isochromophilone IV (7) were isolated from the alga-derived fungus Penicillium sclerotiorum. The structures of isolated azaphilones (1–7) were elucidated by spectrometric identification, especially HRESIMS, CD, and NMR data analyses. Concerning bioactivity, cytotoxic, anti-inflammatory, and anti-fibrosis activities of those isolates were evaluated. As a result, compound 1 showed selective toxicity toward neuroblastoma cell line SH-SY5Y among seven cancer and one fibroblast cell lines. 20 μM of compounds 1, 3, and 7 inhibited the TNF-α-induced NFκB phosphorylation but did not change the NFκB activity. Compounds 2 and 6 respectively promoted and inhibited SMAD-mediated transcriptional activities stimulated by TGF-β.

Azaphilones produced by Penicillium maximae with their cell death-inducing activity on Adriamycin-treated cancer cell

“…The EtOAc soluble fraction was obtained from mycelia and supernatant after incubation of the culture at 28 °C for 20 days. The EtOAc soluble fraction was purified by normal and reversed phase silica gel column chromatography followed by HPLC to give four new compounds: maximazaphilones I–IV ( 1–4 ) together with three known compounds, isochromophilone IV ( 5 ) [ 28 , 29 ], isochromophilone I ( 6 ) [ 30 ], and hypocrellone A ( 7 ) [ 31 ].…”

Anoikis-related genes combined with single cell sequencing: Insights into model specification of lung adenocarcinoma and applicability for prognosis and therapy

“…Despite advances in therapeutic modalities for malignant lung tumors, sundry drugs can result in a poor prognosis because of undesirable side effects, resistance, and cachexia after progression ( Wang et al, 2021 ). Chemoresistance, particularly, remains an important cause of failure of treatment and the driving force of death.…”

Marine natural products

“…213 An untargeted metabolomics approach to examination of a P. restrictum extract led to isolation of pyran-2-one derivatives 578-582, of which 579 was a known synthetic but new NP and 582 was a known terrestrial NP but a rst time marine isolate 214 and P. sclerotiorum yielded azaphilones 583 and 584. 215 Solitumergosterol A 585, is an unique 6/6/6/6/5 steroid obtained from P. solitum from deep-sea sediment, 216 as were polyketide 586 and alkaloids 587 and 588. 217 Penicillium steckii sourced from black band-diseased coral yielded new, 589 and 590, and known epithiodiketopiperazines with an a,b-polysulde bridge that underwent multiple nonenzymatic interconversions in solution.…”