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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Novel 8-hydroxyquinoline derivatives targeting β-amyloid aggregation, metal chelation and oxidative stress against Alzheimer's disease.
Bioorganic & Medicinal Chemistry 2018 July 24
A series of multitargeted 8-hydroxyquinoline derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). In vitro studies indicated that most of the prepared compounds exhibited significant inhibitory effects against self-induced Aβ1-42 aggregation and potential antioxidant properties especially compound 5b (IC50 = 5.64 μM for self-induced Aβ aggregation; the oxygen radical absorbance capacity using fluorescein (ORAC-FL) value is 2.63 Trolox equivalents). Notably, 5b can chelate biometals and inhibit Cu2+ /Zn2+ -induced Aβ1-42 aggregation. The cell assays showed that 5b had excellent protective effects against oxidative toxin H2 O2 and presented low neurotoxicity in PC12 cells. Furthermore, 5b could penetrate the blood-brain barrier (BBB) in vitro and did not show any acute toxicity in mice at doses up to 2000 mg/kg in vivo. Our findings provide a rationale for the potential application of compound 5b as a lead compound in AD therapy.
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