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 1.5-29.9 mu M) and galvinoxyl radicals (IC50 4.9-41.1 mu M) than the lead compound curcumin. Besides, compound 3a could effectively inhibit the Ab 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 (16.7 mg/mL) has also been significantly improved as compared with curcumin (< 0.1 mg/mL). (C) 2013 Elsevier Ltd. All rights reserved.