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

Natchanun Sirimangkalakitti; Lia Dewi Juliawaty; Euis H Hakim; Irpan Waliana; Naoki Saito; Kiyotaka Koyama; Kaoru Kinoshita

doi:10.1016/j.bmcl.2019.05.020

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

Bioorg Med Chem Lett. 2019 Aug 1;29(15):1994-1997. doi: 10.1016/j.bmcl.2019.05.020. Epub 2019 May 14.

Authors

Natchanun Sirimangkalakitti¹, Lia Dewi Juliawaty², Euis H Hakim², Irpan Waliana², Naoki Saito¹, Kiyotaka Koyama¹, Kaoru Kinoshita³

Affiliations

¹ Dementia Drug Resource Development Center, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan.
² Natural Products Chemistry Research Group, Program Study of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung 40132, Indonesia.
³ Dementia Drug Resource Development Center, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan. Electronic address: kaoru@my-pharm.ac.jp.

PMID: 31138471
DOI: 10.1016/j.bmcl.2019.05.020

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.

Keywords: Alzheimer’s disease; Amentoflavone; Anti-Alzheimer agent; Aβ aggregation inhibitory activity; Biflavonoid; Dementia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / pathology
Amyloid beta-Peptides / antagonists & inhibitors*
Biflavonoids / chemistry*
Humans

Substances

Amyloid beta-Peptides
Biflavonoids