2. Academic Validation
  3. 4-Hydroxy-2-pyridone derivatives with antitumor activity produced by mangrove endophytic fungus Talaromyces sp. CY-3

4-Hydroxy-2-pyridone derivatives with antitumor activity produced by mangrove endophytic fungus Talaromyces sp. CY-3

  • Eur J Med Chem. 2024 Apr 5:269:116314. doi: 10.1016/j.ejmech.2024.116314.
Wencong Yang 1,  Bingzhi Zhang 2,  Qi Tan 3,  Yan Chen 4,  Tao Chen 3,  Ge Zou 3,  Bing Sun 3,  Bo Wang 5,  Jie Yuan 6,  Zhigang She 7
Affiliations

Affiliations

  • 1 School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China; School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, PR China.
  • 2 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education, Guangzhou, 510080, PR China.
  • 3 School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China.
  • 4 School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China; School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China.
  • 5 School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China. Electronic address: [email protected].
  • 6 Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education, Guangzhou, 510080, PR China; Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, PR China. Electronic address: [email protected].
  • 7 School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China. Electronic address: [email protected].
PMID: 38527379 DOI: 10.1016/j.ejmech.2024.116314
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 IC50 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.

Keywords

Antitumor; OSMAC; Sambutoxin; Structure-activity relationship; Talaromyces sp..

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