PDF herunterladen
Synlett
DOI: 10.1055/a-2325-3938
letter

Discovery of the Lysosome-Inhibiting Function of Acremolactone B

Autoren

  • Shaonan Wang

    1   School of Pharmacy, East China University of Science and Technology, Shanghai, China (Ringgold ID: RIN47860)

  • Yali Wu

    1   School of Pharmacy, East China University of Science and Technology, Shanghai, China (Ringgold ID: RIN47860)

  • Mengyu Ba

    2   State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Shanghai, China (Ringgold ID: RIN58309)

  • Zhou Xu

    2   State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Shanghai, China (Ringgold ID: RIN58309)

  • Guoxing Gu

    2   State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Shanghai, China (Ringgold ID: RIN58309)

  • William G. Whittingham

    3   Jealott’s Hill International Research Centre, Syngenta UK Ltd, Bracknell, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN10502)

  • Cong Liu

    2   State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Shanghai, China (Ringgold ID: RIN58309)

  • Ang Li 

    2   State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Shanghai, China (Ringgold ID: RIN58309)

  • Weiwei He

    1   School of Pharmacy, East China University of Science and Technology, Shanghai, China (Ringgold ID: RIN47860)
Weitere Informationen
 als PDF herunterladen Alle Artikel dieser Rubrik

Lysosome inhibitors have garnered considerable interest for their utility in lysosome biology research and potential therapeutic applications. We discovered the lysosome-inhibiting function of acremolactone B (1), a scarce azaphilone-type polyketide, leveraging our previous scalable synthesis. This compound significantly reduces lysosomal acidity and impairs the maturation of the lysosomal protease cathepsin D (CTSD) in triple-negative breast cancer cells (MDA-MB-231) and human lung cancer cells (A549). Furthermore, we found that compound 1 suppresses downstream autophagy, as revealed by monitoring autophagic flux and conducting transmission electron microscopy (TEM) analysis. This study unveils the previously unrecognized biological role of 1 and introduces a new scaffold for lysosome inhibitors.



Publikationsverlauf

Eingereicht: 26. April 2024

Angenommen nach Revision: 13. Mai 2024

Accepted Manuscript online:
13. Mai 2024

© . Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany