Antioxidant Capacity Of Curcumin-directed Analogues: Structure-activity Relationship

Curcumin is the active ingredient of turmeric powder with a variety of biological activities including inhibition of lipid peroxidation and free radical scavenging properties. In order to find more active antioxidants with curcumin as the lead compound we synthesized a series of enone analogues of curcumin. This included: (1) curcumin analogues that retained the 7-carbon spacer between the aryl rings; (2) curcumin analogues with a 5-carbon spacer containing a carbonyl group; (3) curcumin analogues with a 5-carbon spacer having both a carbonyl and a saturated five- or six-membered ring. Free radical scavenging activity of curcumin-directed analogues was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH~·) method. The in vitro oxidative haemolysis of human red blood cells (RBCs) was used as a model to study the inhibition effect of these curcumin analogues against free radical-induced lipid peroxidation.It was found that these compounds which bear o-diphenoxyl and o-dimethoxyphenoxyl groups exhibit significantly higher DPPH~·-scavenging and anti-haemolysis activities than those which bear no such groups. In contrast to curcumin analogues that retained the 7-carbon spacer, the compounds with a 5-carbon linker have lower activity. In the case of the latter, the introduction of ring further decreases DPPH~·-scavenging activity. However, the introduction of ring does increase anti-haemolysis activity, suggesting that the lipophilicity of these compounds might play an important role in the antioxidant activity.In addition, we also synthesized curcumin analogues and their antiproliferative effect on human promyelocytic leukemia cells (HL-60) was assessed by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Structure-activity relationship (SAR) analysis demonstrates that the hydroxyl and the methoxy groups on the phenyl ring contribute critically to the cytotoxicity. In contrast to curcumin analogues that retained the 7-carbon and 3-carbon spacer, the compounds with a 5-carbon linker have higher cytotoxicity against HL-60 cells.