2. Academic Validation
  3. Design, synthesis and anti-gastric cancer activity of stable Bisamide curcumin analogues

Design, synthesis and anti-gastric cancer activity of stable Bisamide curcumin analogues

  • Bioorg Chem. 2025 Jul 23:164:108793. doi: 10.1016/j.bioorg.2025.108793.
Jianzhang Wu 1,  Bozhen Wang 2,  Xin Gan 3,  Yuna Wu 4,  Yucan Wu 5,  Xin Liu 6,  Rongjie Hu 7,  Ling Xie 8,  Huaqin Bai 8,  Mingming Jin 7,  Bingqing Fang 7,  Fatehi Khushafah 7,  Tao Wei 9,  Wulan Li 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China; Zhejiang Key Laboratory of Key Technologies for Visual Pathway Reconstruction, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: wjzwzmu@163.com.
  • 2 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; The 1th affiliated hospital of Wenzhou medical university, Wenzhou, Zhejiang 325000, China.
  • 3 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; The 1th affiliated hospital of Wenzhou medical university, Wenzhou, Zhejiang 325000, China; Department of Pharmacy, Ezhou Central Hospital, Ezhou, Hubei 436000, China.
  • 4 State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
  • 5 Zhejiang University-University of Illinois Urbana-Champaign Institute, Zhejiang University, Zhejiang 314400, China.
  • 6 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China; Zhejiang Key Laboratory of Key Technologies for Visual Pathway Reconstruction, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
  • 7 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 8 State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China; Zhejiang Key Laboratory of Key Technologies for Visual Pathway Reconstruction, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
  • 9 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: weitao55@163.com.
  • 10 State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China; Zhejiang Key Laboratory of Key Technologies for Visual Pathway Reconstruction, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; The 1th affiliated hospital of Wenzhou medical university, Wenzhou, Zhejiang 325000, China. Electronic address: lwlwzmu@163.com.
PMID: 40749269 DOI: 10.1016/j.bioorg.2025.108793
Abstract

Curcumin, as a natural product, exhibits notable antitumor activity; however, its further development is limited by poor stability and unfavorable pharmacokinetic properties. To enhance the stability and pharmacological activity of curcumin, a series of stable bisamide curcumin analogs were designed and synthesized through amide bond introduction. Several compounds demonstrated high efficacy in suppressing the proliferation of gastric Cancer cells in vitro. The quantitative structure-activity relationship models (QSAR) of compounds were established by random forest algorithm and R2 in two gastric Cancer cells were greater than 0.9. The most promising active compound KB-15 significantly inhibits proliferation, cell colony formation, and migration in both AGS and BGC-823 cells in a concentration dependent manner. Additionally, KB-15 was found to induce cell cycle arrest and promote Apoptosis. In a BGC-823 xenograft mouse model, KB-15 demonstrated robust inhibitory activity on gastric Cancer growth in vivo. Mechanistic studies revealed that KB-15 exerts its antitumor effects by inhibiting STAT3 phosphorylation and downregulating HO-1 expression. Compared with curcumin, KB-15 demonstrated significantly enhanced stability and improved pharmacokinetic parameters. In summary, this study presents a promising series of bisamide curcumin analogs, with KB-15 being a potential candidate for further development as an antitumor drug.

Keywords

Antitumor; Bisamide; Curcumin; ROS; STAT3.

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