Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.
Posted by rob on August 24, 2010 under Uncategorized | 
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Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.
Bioorg Med Chem. 2010 Aug 1;
Authors: Yadav B, Taurin S, Rosengren RJ, Schumacher M, Diederich M, Somers-Edgar TJ, Larsen L
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 EC(50) values below 1muM and inhibition of NF-kappaB activation below 7.5muM. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18h. 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.
PMID: 20728364 [PubMed - as supplied by publisher]