ABSTRACT
Curcumin, a bis-α, ß-unsaturated ß-diketon dietary compound from turmeric, is among the most promising dietary compounds for preventing chronic diseases. Previous research has shown that curcumin is highly reactive toward protein thiols to form curcumin-protein adducts, however, the interactions of curcumin with proteins are under-studied. Here we report the design and synthesis of "click" chemistry probes of curcumin, mono-propargyl curcumin (mono-Cur) and di-propargyl curcumin (di-Cur), and use the click probes to study curcumin-proteins interactions in vitro and in vivo. We find that compared with di-Cur, the mono-Cur probe has more potent biological effects and enhanced effects to label proteins in cultured cells, suggesting that mono-Cur is a better click probe to study the biological actions of curcumin. Furthermore, using the mono-Cur probe, we find that oral administration of this probe in mice leads to formation of curcumin-protein adducts in colon and liver tissues of C57BL/6 mice, suggesting that curcumin could covalently modify cellular proteins in vivo. Together, these results could help us to better understand protein-curcumin interactions. These results could in part explain the poor pharmacokinetics of curcumin; in addition, formation of these protein adducts could contribute to the health-promoting effects of curcumin.