title: Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.
abstract: A series of 18 heterocyclic cyclohexanone analogues of curcumin have been synthesised and screened for their activity in both adherent and non-adherent cancer cell models. Cytotoxicity towards MBA-MB-231 breast cancer cells, as well as ability to inhibit NF-kappaB transactivation in non-adherent K562 leukemia cells were investigated. Three of these analogues 3,5-bis(pyridine-4-yl)-1-methylpiperidin-4-one B1, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one B10, and 8-methyl-2,4-bis((pyridine-4-yl)methylene)-8-aza-bicyclo[3.2.1]octan-3-one C1 showed potent cytotoxicity towards MBA-MB-231, MDA-MB-468, and SkBr3 cell lines with EC50 values below 1 microM and inhibition of NF-kappaB activation below 7.5 microM. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18 h. This level of activity warrants further investigation for the treatment of ER-negative breast cancer and/or chronic myelogenous leukemia as prototypical cellular models for solid and liquid tumors.
authors: Department of Pharmacology & Toxicology, University of Otago, Dunedin, New Zealand.
authors: Babasaheb
authors: B
authors: Yadav
authors: Sebastien
authors: S
authors: Taurin
authors: Rhonda J
authors: RJ
authors: Rosengren
authors: Marc
authors: M
authors: Schumacher
authors: Marc
authors: M
authors: Diederich
authors: Tiffany J
authors: TJ
authors: Somers-Edgar
authors: Lesley
authors: L
authors: Larsen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives*; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D016328:NF-kappa B / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003512:Cyclohexanones; D006571:Heterocyclic Compounds; D016328:NF-kappa B; C036468:cyclohexanone; D003474:Curcumin