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A novel series of gardenamide A derivatives was synthesized as potential anti-Alzheimer's disease agents. The neuroprotective effects of these multifunctional agents against oxygen-glucose deprivation (OGD)-induced neurotoxicity in rat cortical neurons, and hydrogen peroxide (H 2 O 2 )- and amyloid-β 1-42 (Aβ 1-42 )-induced neurotoxicity in rat hippocampal neurons were evaluated. In vitro studies revealed that these compounds demonstrated moderate to good multifunctional neuroprotective activity. Among the entire series, compounds 10e , 10j , 10n and 10p appeared to be the most active multifunctional neuroprotective agents. Studies indicate that compounds 10e , 10f , 10h , 10i , 10j , 10n and 10p exhibit significant activities against OGD-induced neurotoxicity in rat cortical neurons, and 10e , 10j , 10n and 10p show prominent activities against H 2 O 2 - and Aβ 1-42 -induced neurotoxicity in rat hippocampal neurons. Moreover, these derivatives did not exert conspicuous neurotoxicity in rat cortical neurons. Thus, the present study evidently shows that 10e , 10j , 10n and 10p are potent multifunctional neuroprotective agents, which may serve as promising lead candidates for anti-Alzheimer's disease drug development.

The synthesis and biological evaluation of novel gardenamide A derivatives as multifunctional neuroprotective agents