Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin |
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Authors: | Babasaheb Yadav Sebastien Taurin Rhonda J. Rosengren Marc Schumacher Marc Diederich Tiffany J. Somers-Edgar Lesley Larsen |
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Affiliation: | 1. Department of Pharmacology & Toxicology, University of Otago, Dunedin, New Zealand;2. Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Luxembourg;3. The New Zealand Institute for Plant and Food Research Ltd, Dunedin, New Zealand |
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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-κB 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 μM and inhibition of NF-κB activation below 7.5 μM. 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. |
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