2. Academic Validation
  3. Design, synthesis and bioactivity evaluation of parthenolide-chalcone hybrids as potential anti-lung cancer agents

Design, synthesis and bioactivity evaluation of parthenolide-chalcone hybrids as potential anti-lung cancer agents

  • Bioorg Chem. 2025 Sep:164:108808. doi: 10.1016/j.bioorg.2025.108808.
Yongping Bai 1,  Junqi Wang 2,  Weinan Li 2,  Ning Liu 3,  Kun Liu 2,  Hui Li 2,  Yihao Zhao 2,  Xiyan Duan 4,  Yahui Ding 5
Affiliations

Affiliations

  • 1 College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China.
  • 2 School of Chemistry & Chemical Engineering, Henan University of Science and Technology, Luoyang 471003, Henan, China.
  • 3 School of Nursing, Henan University of Science and Technology, Luoyang 471003, Henan, People's Republic of China.
  • 4 School of Chemistry & Chemical Engineering, Henan University of Science and Technology, Luoyang 471003, Henan, China. Electronic address: duanxiyan@tju.edu.cn.
  • 5 College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China; College of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, People's Republic of China. Electronic address: 017095@nankai.edu.cn.
PMID: 40763598 DOI: 10.1016/j.bioorg.2025.108808
Abstract

Natural products are valuable resources in drug discovery. To improve the activity of parthenolide, 49 parthenolide-chalcone hybrids were designed and synthesized. The activity evaluation suggested compound 10d exhibited the most potent Anticancer activity with an IC₅₀ of 0.11 μM, 40.9-fold improvement compared with parthenolide. Besides that, compound 10d induced Apoptosis, inhibited cell migration and proliferation. The mechanistic studies revealed that 10d may directly bind to Cys416 of ALOX5 (Arachidonate 5-lipoxygenase) and enhance its protein stability, then inhibited β-catenin protein levels and eventually suppressed STAT3 (Signal Transducer and Activator of Transcription 3) signal pathway. Moreover, water-soluble prodrug of 10d significantly inhibited tumor growth in lung Cancer patient-derived xenograft (PDX) model without notable toxicity. These findings suggested that 10d could be considered as a promising ALOX5-targeting Anticancer candidate worthy of further development.

Keywords

ALOX5; Anti-cancer activity; Apoptosis; Chalcone; Parthenolide.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z