Design, synthesis, and anti-cancer evaluation of C-14 arylcarbamate derivatives of andrographolide
Journal
Bioorganic & medicinal chemistry
Journal Volume
98
Date Issued
2024-01-15
Author(s)
Yang, Tzu-Ching
Chiang, Yun-Jou
Chiang, Po-Yu
Chen, Han-Yu
Zhuang, Kai-Ru
Wang, Yu-Chia
Lin, Chao-Hsiung
Fu, Shu-Ling
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.
Subjects
Andrographolide; Anticancer; Covalent; Cytotoxicity; Electrophilic; Natural product
SDGs
Type
journal article