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.
- 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: [email protected].
- 7. Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan. Electronic address: [email protected].
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.