Controllable conformation and reactivity of bicyclic α-methylene cyclopentanones and their NF-κB pathway inhibitory activity

Kohyama, Aki; Shiuchi, Aya; Zhou, Yue; Tanioka, Masaru; Sugimoto, Kenji; Sakurai, Hiroaki; Matsuya, Yuji

doi:10.1039/d3ob00357d

Cited by 1 publication

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“…[ 16‐18 ] As a result, the reduction of keratinocyte hyperproliferation and excessive inflammation through inhibiting TNF‐ α is instrumental in the treatment of psoriasis. [ 19‐22 ] Monoclonal antibodies targeting TNF‐ α, such as etanercept, have been developed for widespread clinical treatment of autoimmune and auto‐inflammatory diseases, including rheumatoid arthritis and psoriasis. [ 23‐25 ] However, biological macromolecule drugs still have the disadvantages of high cost, low adaptability, and more susceptibility to infection after long‐term use.…”

Section: Background and Originality Contentmentioning

confidence: 99%

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

Hu,

Li,

Shi

et al. 2023

Chin. J. Chem.

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Comprehensive SummaryPsoriasis is a chronic immune‐mediated inflammatory skin disease and the TNF‐α is an important therapeutic target of this disease. In our continuous study of bioactive natural products from fungi, the first ergosterol‐polyether adducts, polyaspers A (1) and B (2), along with two known ergosterols, (3β,5α,6α,22E)‐5,6‐epoxy‐3‐hydroxyergosta‐8,22‐dien‐7‐one (3) and calvasterol B (4), were isolated from Aspergillus sp. TJ507. Structure elucidation was accomplished by extensive spectroscopic analysis and single‐crystal X‐ray diffraction tests. Polyaspers A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system, and their biosynthetic pathways were proposed to include intermolecular cyclization and Diels‐Alder reactions. Activity screen of these isolates showed that 1—3 could improve the cell viability in an actinomycin D/TNF‐α induced L929 cells death model, with the EC50 values of 49.85, 46.75 and 4.99 μmol/L, respectively, and the activity of 3 was even comparable with that of the positive control SPD304. Further bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF‐α in HaCaT cells. In an imiquimod‐induced psoriasis murine model, 3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL‐17 and IL‐23, presenting an anti‐psoriatic effect. As such, those ergosterol derivatives, might serve as lead compounds for the development of novel TNF‐α inhibitory agents in the clinical treatment of psoriasis.

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Section: Background and Originality Contentmentioning

confidence: 99%

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

Hu,

Li,

Shi

et al. 2023

Chin. J. Chem.

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Controllable conformation and reactivity of bicyclic α-methylene cyclopentanones and their NF-κB pathway inhibitory activity

Abstract: Tuning the electrophilicities of Michael acceptors is important for the development of targeted covalent drugs. To this end, the electronic effects of the electrophilic structures have been well investigated, but...

Cited by 1 publication

References 21 publications

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

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