title: Cytotoxicity against cholangiocarcinoma cell lines of zerumbone derivatives.
abstract: 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 IC(50) value of 16.44 microM. 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.
authors.affiliation: Natural Products Research Unit, Center for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Uraiwan
authors.initials: U
authors.lastname: Songsiang
authors.forename: Siripit
authors.initials: S
authors.lastname: Pitchuanchom
authors.forename: Chantana
authors.initials: C
authors.lastname: Boonyarat
authors.forename: Chariya
authors.initials: C
authors.lastname: Hahnvajanawong
authors.forename: Chavi
authors.initials: C
authors.lastname: Yenjai
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000473:pathology*; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C403304:zerumbone; D066246:ErbB Receptors