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ID: ALA4387742

Journal: Bioorg Med Chem Lett

Title: Naturally occurring biflavonoids with amyloid β aggregation inhibitory activity for development of anti-Alzheimer agents.

Authors: Sirimangkalakitti N, Juliawaty LD, Hakim EH, Waliana I, Saito N, Koyama K, Kinoshita K.

Abstract: Amyloid β (Aβ) aggregation plays an essential role in promoting the progression of Alzheimer's disease (AD). Therefore, the inhibition of Aβ aggregation is a potential therapeutic approach for AD. Herein, twenty-seven biflavonoids with different inter-flavonyl linkages and methoxy substitution patterns were isolated from several plants, and their Aβ40 aggregation inhibitory activity was evaluated by the thioflavin-T fluorescence assay. Amentoflavone (1) and its monomethoxy derivatives (2, 3, and 5) exhibited the most potent inhibitory activity, with IC50 values of approximately 5 μM. It was clarified that increasing the number of methoxy substituents on the biflavonoid structures attenuated the inhibitory activity. Moreover, the linkage and the methoxy substitution pattern had a marked influence on the inhibitory activity. Our investigation strongly supports that biflavonoids can be considered a new type of anti-Alzheimer agents that may be successfully developed for AD patients.

CiteXplore: 31138471

DOI: 10.1016/j.bmcl.2019.05.020