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4-Hydroxy-2-pyridone derivatives with antitumor activity produced by mangrove endophytic fungus Talaromyces sp. CY-3.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2024 Apr 05; Vol. 269, pp. 116314. Date of Electronic Publication: 2024 Mar 16. - Publication Year :
- 2024
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Abstract
- OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1-2, 4, 8-9), together with seven known compounds (3, 5-7, 10-12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds 1-12 showed cytotoxicity to tumor cell lines with IC <subscript>50</subscript> values in the range of 1.76-49.13 μM. The antitumor molecular mechanism of 10 was also explored. In vitro compound 10 significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that 10 could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects in vitro is that 10 arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity.<br />Competing Interests: Declaration of competing interest All authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence this work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.<br /> (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 269
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38527379
- Full Text :
- https://doi.org/10.1016/j.ejmech.2024.116314