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Design, synthesis and evaluation of a novel metal chelator as multifunctional agents for the treatment of Alzheimer's disease. | LitMetric
A series of compounds following the lead compounds including deferasirox and tacrine were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease (AD). In vitro studies showed that most synthesized compounds exhibited good multifunctional activities in inhibiting acetylcholinesterase (bAChE), and chelating metal ions. Especially, compound TD demonstrated significant metal chelating property, a moderate acetylcholinesterase (AChE) inhibitory activity and an antioxidant activity. Results from the molecular modeling indicated that TD compounds were mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of TcAChE. Moreover, TD showed a low cytotoxicity but a good protective activity against the injury caused by HO. These results suggest that TD compounds might be considered as attractive multi-target cholinesterase inhibitor and will play important roles in the treatment of AD.
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