Design, synthesis and anti-Alzheimer properties of dimethylaminomethyl-substituted curcumin derivatives.

Eight dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized. The antioxidant test revealed that the synthesized compounds had higher free radical scavenging activity towards both 2,2-diphenyl-1-picrylhydrazyl free radicals (DPPH) (IC50 1.5-29.9μM) and galvinoxyl radicals (IC50 4.9-41.1μM) than the lead compound curcumin. Besides, compound 3a could effectively inhibit the Aβ self-aggregation in vitro. Investigated in phosphate-buffered solutions (pH=7.4) in the presence or absence of 0.1% FBS 3a showed a good stability while curcumin did not. Furthermore, 3a showed a good lipophilicity (logP=3.48), suggesting a potential ability to penetrate the blood-brain-barrier. The aqueous solubility of the hydrochloride salt of 3a (16.7mg/mL) has also been significantly improved as compared with curcumin (<0.1mg/mL).