Synthesis, Isolation and Biological Evaluation of a New Active Quinone Methide Derived Curcuminoid

A new curcuminoid, quinone methide cyclopentadione (QMC), was synthesized by oxidation of curcumin (CUR) in the presence of potassium ferricyanide, and further isolated and analyzed. QMC was found to be a relatively water-soluble curcuminoid, and more stable than CUR in citric-phosphate buffer solutions. Unlike CUR, QMC possesses a pH-independent stability. In plasma, QMC was degraded by 50% after 8 hours and reached 30% of its initial concentration after 48h, while CUR was thoroughly decomposed. It has been demonstrated that QMC has a similar anti-proliferative activity as CUR in three different cancer cell lines- MCF-7, PC3 and HT29. Molecular examination of QMC in cancer cells exhibited similar effect to CUR on two transcription factors, Nrf-2 and NF-κB. An anti-inflammatory activity of QMC was demonstrated by measuring MCP-1 secretion levels in TNFα-induced human keratinocytes cell culture, which had been pre-treated with either CUR or QMC. This report presents the advantages of the new quinone methide derived curcuminoid and its pharmaceutical potential as an alternative to the poorly soluble curcumin.