Development of naringenin--alkylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease.

In this study, a series of naringenin--alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The biological activity results revealed that compounds and showed good antioxidant activity with ORAC values of 2.3 and 1.2, respectively. Compounds and were reversible and excellent AChE inhibitors with IC values of 0.91 μM and 0.57 μM, respectively. Moreover, compounds and could inhibit self-induced A aggregation with 62.1% and 43.8% inhibition rate, respectively, and significantly inhibited AChE-A aggregation with 51.7% and 43.4% inhibition rate, respectively. In addition, compounds and were selective metal chelators and remarkably inhibited Cu-induced A aggregation with 73.5% and 68.7% inhibition rates, respectively. Furthermore, compounds and could cross blood-brain barrier and displayed good neuroprotective effects and anti-inflammatory properties. Further investigation showed that compound did not show obvious hepatotoxicity and displayed a good hepatoprotective effect by its antioxidant activity. The study displayed that compound significantly improved scopolamine-induced mice memory impairment. Therefore, compound was a potential multifunctional candidate for the treatment of AD.