2. Academic Validation
  3. Discovery of tetrahydrothiazolopyridine-incorporated curcumol derivatives as novel and highly potent anti-cancer agents

Discovery of tetrahydrothiazolopyridine-incorporated curcumol derivatives as novel and highly potent anti-cancer agents

  • Eur J Med Chem. 2026 Feb 15:304:118531. doi: 10.1016/j.ejmech.2025.118531.
Shixun Guo 1,  Yuhang Fan 1,  Wei Li 1,  Kailin Lu 1,  Qiang Wang 1,  Chong Meng 1,  Yuxuan Tong 1,  Jian Li 1,  Jinlian Wei 2,  Yongqiang Zhang 3
Affiliations

Affiliations

  • 1 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China.
  • 2 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
  • 3 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
PMID: 41478006 DOI: 10.1016/j.ejmech.2025.118531
Abstract

Herein, the structural modification of curcumol via a privileged scaffold incorporation strategy has been demonstrated, which enables the production of a class of novel tetrahydrothiazolopyridine-containing derivatives. Among them, the analogs with an ortho- or meta-substituted benzoyl exhibited superior in vitro anti-proliferative activity, and 9b with a 2, 3-dimethylbenzoyl group showed the most potent activity and good selectivity. Furthermore, 9b showed good in vivo anti-cancer activity and could efficiently suppress the migration of Cancer cells, while no apparent toxicity was observed. Further mechanistic studies revealed that 9b exhibited an ability to induce G2/M-phase arrest in Cancer cells associated with the disruption of tubulin polymerization. In particular, 9b could efficiently repress self-renewal of Cancer Stem Cells. Overall, our findings highlight 9b as a promising lead compound in Cancer therapy.

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