2. Academic Validation
  3. Design, synthesis, and anti-cancer evaluation of C-14 arylcarbamate derivatives of andrographolide

Design, synthesis, and anti-cancer evaluation of C-14 arylcarbamate derivatives of andrographolide

  • Bioorg Med Chem. 2024 Jan 15:98:117582. doi: 10.1016/j.bmc.2023.117582.
Tzu-Ching Yang 1,  Yun-Jou Chiang 2,  Po-Yu Chiang 1,  Han-Yu Chen 1,  Kai-Ru Zhuang 3,  Yu-Chia Wang 4,  Chao-Hsiung Lin 5,  Lee-Chiang Lo 6,  Shu-Ling Fu 7
Affiliations

Affiliations

  • 1 Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
  • 2 Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 3 Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 4 Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 5 Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 6 Department of Chemistry, National Taiwan University, Taipei 106, Taiwan. Electronic address: lclo@ntu.edu.tw.
  • 7 Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan. Electronic address: slfu@nycu.edu.tw.
PMID: 38171253 DOI: 10.1016/j.bmc.2023.117582
Abstract

In this study, we explored a concise and mild synthetic route to produce novel C-14 arylcarbamate derivatives of andrographolide, a known anti-inflammatory and Anticancer natural product. Upon assessing their anti-cancer efficacy against pancreatic ductal adenocarcinoma (PDAC) cells, some derivatives showed stronger cytotoxicity against PANC-1 cells than andrographolide. In addition, we demonstrated one derivative, compound 3m, effectively reduced the expression of oncogenic p53 mutant proteins (p53R273H and p53R248W), proliferation, and migration in PDAC lines, PANC-1 and MIA PaCa-2. Accordingly, the novel derivative holds promise as an anti-cancer agent against pancreatic Cancer. In summary, our study broadens the derivative library of andrographolide and develops an arylcarbamate derivative of andrographolide with promising Anticancer activity against PDAC.

Keywords

Andrographolide; Anticancer; Covalent; Cytotoxicity; Electrophilic; Natural product.

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