Synthesis and Pharmacological Evaluation of novel chromone derivatives as balanced multifunctional agents against Alzheimer's disease

Publication date: Available online 17 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Fan Li, Jia-Jia Wu, Jin Wang, Xue-Lian Yang, Pei Cai, Qiao-Hong Liu, Ling-Yi Kong, Xiao-Bing Wang
In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of chromone derivatives were designed, synthesized and evaluated. In vitro assay indicated that most of the target compounds have both MAOs inhibition activities, antioxidant activity and biometal chelating ability. Especially, compound s19 exhibits good inhibitory potency for inhibition of MAOs (IC50 value of 5.12 μM for hMAO-A and 0.816 μM for hMAO-B), moderate inhibition of Aβ aggregation (75.1% at 20 μM), metal chelation, control of ROS generation and antioxidant activity (ORAC = 3.62). In addition, s19 could reduce PC12 cells death induced by oxidative stress and penetrate the blood–brain barrier (BBB). Taken together, these results suggested that s19 might be a promising multitargeted compound for AD treatment.

Graphical abstract

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