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

Tzu-Ching Yang; Yun-Jou Chiang; Po-Yu Chiang; Han-Yu Chen; Kai-Ru Zhuang; Yu-Chia Wang; Chao-Hsiung Lin; Lee-Chiang Lo; Shu-Ling Fu

doi:10.1016/j.bmc.2023.117582

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. Epub 2023 Dec 28.

Authors

Tzu-Ching Yang¹, Yun-Jou Chiang², Po-Yu Chiang¹, Han-Yu Chen¹, Kai-Ru Zhuang³, Yu-Chia Wang⁴, Chao-Hsiung Lin⁵, Lee-Chiang Lo⁶, Shu-Ling Fu⁷

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 (p53^R273H and p53^R248W), 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.

MeSH terms

Carcinoma, Pancreatic Ductal* / pathology
Cell Line, Tumor
Diterpenes* / pharmacology
Humans
Pancreatic Neoplasms* / pathology
Tumor Suppressor Protein p53 / metabolism

Substances

andrographolide
Tumor Suppressor Protein p53
Diterpenes