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

被引：22

作者：

Sirimangkalakitti, Natchanun ^{[1
]}

Juliawaty, Lia Dewi ^{[2
]}

Hakim, Euis H. ^{[2
]}

Waliana, Irpan ^{[2
]}

Saito, Naoki ^{[1
]}

Koyama, Kiyotaka ^{[1
]}

Kinoshita, Kaoru ^{[1
]}

机构：

[1] Meiji Pharmaceut Univ, Dementia Drug Resource Dev Ctr, 2-522-1 Noshio, Kiyose, Tokyo 2048588, Japan

[2] Inst Teknol Bandung, Program Study Chem, Nat Prod Chem Res Grp, Fac Math & Nat Sci, Jalan Ganesha 10, Bandung 40132, Indonesia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 15期

关键词：

Biflavonoid; Amentoflavone; A beta aggregation inhibitory activity; Anti-Alzheimer agent; Alzheimer's disease; Dementia; CYTOTOXIC BIFLAVONOIDS; AMENTOFLAVONE; HINOKIFLAVONE; LEAVES; PRODUCTS; BRAIN;

D O I：

10.1016/j.bmcl.2019.05.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Amyloid beta (A beta) aggregation plays an essential role in promoting the progression of Alzheimer's disease (AD). Therefore, the inhibition of A beta 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 A beta(40) 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 mu M. 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.

引用

页码：1994 / 1997

页数：4

共 44 条

[1] Structural requirements for the flavonoid fisetin in inhibiting fibril formation of amyloid β protein
Akaishi, Tatsuhiro
Morimoto, Takeo
Shibao, Mami
Watanabe, Sayaka
Sakai-Kato, Kumiko
Utsunomiya-Tate, Naoko
Abe, Kazuho
[J]. NEUROSCIENCE LETTERS, 2008, 444 (03) : 280 - 285
[2] STRUCTURES OF NATURALLY OCCURRING BIFLAVONYLS
BAKER, W
ROBINSON, KW
FINCH, ACM
OLLIS, WD
[J]. JOURNAL OF THE CHEMICAL SOCIETY, 1963, (MAR): : 1477 - &
[3] COMPONENTS OF METASEQUOIA-GLYPTOSTROBOIDES .3. BIFLAVONES AND 2,3-DIHYDROBIFLAVONES FROM METASEQUOIA-GLYPTOSTROBOIDES
BECKMANN, S
GEIGER, H
DEGROOTP.W
[J]. PHYTOCHEMISTRY, 1971, 10 (10) : 2465 - &
[4] Molecular mechanism of Thioflavin-T binding to amyloid fibrils
Biancalana, Matthew
Koide, Shohei
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2010, 1804 (07): : 1405 - 1412
[5] Amentoflavone Ameliorates Aβ1-42-Induced Memory Deficits and Oxidative Stress in Cellular and Rat Model
Chen, Chao
Li, Bin
Cheng, Guangqing
Yang, Xiaoni
Zhao, Ningning
Shi, Ran
[J]. NEUROCHEMICAL RESEARCH, 2018, 43 (04) : 857 - 868
[6] Amyloid-β aggregation
Finder, Verena H.
Glockshuber, Rudi
[J]. NEURODEGENERATIVE DISEASES, 2007, 4 (01) : 13 - 27
[7] THE STRUCTURE OF HINOKIFLAVONE, A NEW TYPE BISFLAVONOID
FUKUI, Y
KAWANO, N
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1959, 81 (23) : 6331 - 6331
[8] Sciadopitysin: active component from Taxus chinensis for anti-Alzheimer's disease
Gu, Qiong
Li, Yanping
Chen, Yingchun
Yao, Peifen
Ou, Tianmiao
[J]. NATURAL PRODUCT RESEARCH, 2013, 27 (22) : 2157 - 2160
[9] Transport of amentoflavone across the blood-brain barrier in vitro
Gutmann, H
Bruggisser, R
Schaffner, W
Bogman, K
Botomino, A
Drewe, J
[J]. PLANTA MEDICA, 2002, 68 (09) : 804 - 807
[10] 5,5]-DIHYDROXY-7,4],7]]4]]]-TETRAMETHOXY-8,3]]]-BIFLAVONE FROM DACRYDIUM CUPRESSINUM LAMB
HODGES, R
[J]. AUSTRALIAN JOURNAL OF CHEMISTRY, 1965, 18 (09) : 1491 - &

← 1 2 3 4 5 →