Design, synthesis, and biological activity evaluation of BACE1 inhibitors with antioxidant activity.

The proteolytic enzyme beta-secretase (BACE1) plays a central role in the synthesis of the pathogenic beta-amyloid peptides (A beta) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1-D18) with free radical-scavenging activities were synthesized by molecular hybridization of 2-aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 '-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS(+center dot)) assay, which could be used as a lead compound for further study.