Cytotoxicity against cholangiocarcinoma cell lines of zerumbone derivatives

Cholangiocarcinoma (CCA) is an aggressive malignancy with a very high morbidity and mortality for which an effective treatment is lacking. In this study, seventeen zerumbone derivatives were synthesized and evaluated for in vitro cytotoxicity against cholangiocarcinoma cell lines. 5 showed the most potent antiproliferative activity against KKU-100 cell line with an IC50 value of 16.44 μM. To investigate the potential molecular target of the most active compound, the docking was performed using different enzymes and receptor proteins including CDK-2, CDK-5, EGFR, and GSK-3. The docking results revealed that 5 exhibited better binding interaction to EGFR than CDK-2, CDK-5 and GSK-3. All results indicate that 5 should be a promising candidate for treatment of cancer.

Graphical abstractAmine 5 modified from zerumbone (1) exhibited very strong cytotoxicity against cholangiocarcinoma cells (KKU-100; the least sensitive cells) with IC50 values of 16.44 μM. The docking experiment showed that 5 exhibited better binding interaction to EGFR than CDK-2, CDK-5 and GSK-3.Figure optionsDownload full-size imageDownload as PowerPoint slide