Aminoalkyl-Substituted Flavonoids: Synthesis, Cholinesterase Inhibition, Β-Amyloid Aggregation, and Neuroprotective Study Publisher



Faraji L¹ ; Nadri H² ; Moradi A² ; Bukhari SNA³ ; Pakseresht B⁴ ; Moghadam FH⁵ ; Moghimi S¹ ; Abdollahi M^{1, 6} ; Khoobi M^{1, 7} ; Foroumadi A^{8, 9}
Source: Medicinal Chemistry Research Published:2019

Abstract

In this manuscript, 17 aminoalkyl-substituted flavonoid derivatives were synthesized and their anticholinesterase, anti-beta-amyloid (Aβ) aggregation and neuroprotective activities were evaluated. The synthesized compounds were prepared through four-step reaction, started from the reaction between 2-hydroxyacetophenone and 4-methoxy benzaldehyde. Among the final compounds, 6j displayed the best anti-butyrylcholinesterase activity (IC50 = 0.335 μM). Moreover, compound 6i significantly protected PC12 neurons against H2O2-induced cell death. This compound could also inhibit acetylcholinesterase and self-induced Aβ peptide aggregation by 51.3% and 49.2%, respectively. The results indicated that compound 6i could be considered as a lead compound towards the discovery of disease-modifying drugs for Alzheimer’s disease (AD) therapy. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.