Chain breaking antioxidant activity of new synthetic analogues of curcumin as individuals and in mixtures with conventional antioxidants

The effectiveness of development of new biologically active compounds with antioxidant potential has been proved in the treatment of various diseases. The design of new synthetic analogues which combine minimal toxicity, stability and improved biological properties compared to the parent compound has always been of interest for medicinal chemistry. Curcumin is one of the most powerful natural bio-antioxidants but unfortunately its poor bioavailability and instability at physiological level is a serious disadvantage. Previously, we observed high antiproliferative and apoptotic activity of C2-symmetry hydroxylated biphenyls curcuminanalogues against malignant melanoma [1]. We hypothesized that the presence of a biphenyl scaffold in a curcumin structure would control rigidity at the two aromatic rings and thus play an important role in enhancing antitumoral activity. Herein we have extended the synthesis of biphenyls-curcuminoids and their corresponding monomers. Chain-breaking antioxidant activity of the studied compounds is evaluated during bulk phase lipid autoxidation at 80 oC. Compounds that exhibit weak to moderate antioxidant activity were tested in mixture with stronger antioxidants. Synergism and antagonism of mixtures were assessed and discussed. All structures are optimized at UB3LYP/6-31+G(d,p) level in gas phase to explain the structure-activity relationships