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

被引：21

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

[21] Cytotoxic biflavonoids from Selaginella delicatula
Lin, LC
Kuo, YC
Chou, CJ
[J]. JOURNAL OF NATURAL PRODUCTS, 2000, 63 (05): : 627 - 630
[22] Lone SH, 2016, BIFLAVANOIDS: CHEMICAL AND PHARMACOLOGICAL ASPECTS, P37
[23] LOPEZSAEZ JA, 1994, Z NATURFORSCH C, V49, P267
[24] Madhav R., 2017, TETRAHEDRON LETT, V1969, P10
[25] MARKHAM KR, 1987, PHYTOCHEMISTRY, V26, P3335, DOI 10.1016/S0031-9422(00)82499-1
[26] MASHIMA T, 1970, TETRAHEDRON LETT, P2937, DOI 10.1016/S0040-4039(01)98378-9
[27] MIURA H, 1969, CHEM PHARM BULL, V17, P150
[28] MIURA H, 1968, Yakugaku Zasshi, V88, P1489
[29] MIURA H, 1966, CHEM PHARM BULL, V14, P1404
[30] MIURA HIROSHL, 1967, YAKUGAKU ZASSHI J PHARM SOC JAP, V87, P871

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