title: Novel 3,5-bis(arylidene)-4-piperidone dimers: potent cytotoxins against colon cancer cells.
abstract: Two novel series of dimeric 3,5-bis(arylidene)-4-piperidones 7 and 8 were prepared as cytotoxic agents. A specific objective of this study was the discovery of novel compounds displaying potent anti-proliferative activities against colon cancers. Most of the compounds demonstrate potent cytotoxicity against HCT116 and HT29 colon cancer cell lines in which the IC50 values range from low micromolar to nanomolar values. In general, the majority of the compounds showed greater cytotoxicity and some degree of selectivity toward HCT116 cells compared to HT29 cells. Compound 9 in which the amidic carbonyl groups were excised was substantially less potent than 8a in both cell lines suggested that the amide groups are important components of the molecules for exhibiting cytotoxicity. Virtually all the compounds were more potent than a reference drug 5-fluorouracil which is used in treating colon cancers as well as a related enone curcumin. QSAR studies were undertaken and some guidelines for amplification of the project have been formulated. Flow cytometry analysis of a representative potent compound 7f revealed that it induces apoptosis in HCT116 cells.
authors: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada.
authors: Swagatika
authors: S
authors: Das
authors: Umashankar
authors: U
authors: Das
authors: Deborah
authors: D
authors: Michel
authors: Dennis K J
authors: DK
authors: Gorecki
authors: Jonathan R
authors: JR
authors: Dimmock
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D010881:Piperidones