Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits

被引：59

作者：

Cho, Jung Keun ^{[1
]}

Ryu, Young Bae ^{[3
]}

Curtis-Long, Marcus J. ^{[2
]}

Ryu, Hyung Won ^{[1
]}

Yuk, Heung Joo ^{[1
]}

Kim, Dae Wook ^{[1
]}

Kim, Hye Jin ^{[1
]}

Lee, Woo Song ^{[3
]}

Park, Ki Hun ^{[1
]}

机构：

[1] Gyeongsang Natl Univ, Grad Sch, Div Appl Life Sci, IALS,Program BK21, Jinju 660701, South Korea

[2] Brandeis Univ, Grad Program Biochem & Biophys, Woltham, MA 02453 USA

[3] KRIBB, Ecofriendly Biomat Res Ctr, Jeongeup 580185, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 08期

基金：

新加坡国家研究基金会;

关键词：

Human acetylcholinesterase; Butyrylcholinesterase; Time-dependent inhibitor; Fluorescence quenching; Paulownia tomentosa; MEDIATED NEUROPROTECTION; DONEPEZIL; KINETICS; RIVASTIGMINE; GALANTAMINE; DISEASE;

D O I：

10.1016/j.bmc.2012.02.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease is rapidly becoming one of the most prevalent human diseases. Inhibition of human acetylcholinestrase (hAChE) and butyrylcholinestrase (BChE) has been linked to amelioration of Alzheimer's symptoms and research into inhibitors is of critical importance. Purification of the methanol extract of Paulownia tomentosa fruits yielded potent hAChE and BChE inhibitory flavonoids (1-9). A comparative activity screen indicated that a geranyl group at C6 is crucial for both hAChE and BChE. For example, diplacone (8) showed 250-fold higher efficacy than its parent eriodictyol (12). IC(50)s of diplacone (8) were 7.2 mu M for hAChE and 1.4 mu M for BChE. Similar trends were also observed for 4'-O-methyldiplacone (4) (vs its parent, hesperetin 10) and mimulone (7) (vs its parent, naringenin 11). Representative inhibitors (1-8) showed mixed inhibition kinetics as well as time-dependent, reversible inhibition toward hAChE. The binding affinities of these compounds to hAChE were investigated by monitoring quenching of inherent enzyme fluorescence. The affinity constants (K-SA) increased in proportion to inhibitory potencies. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2595 / 2602

页数：8

共 25 条

[1] An open-label, comparative study of rivastigmine, donepezil and galantamine in a real-world setting [J].

Aguglia, E ;

Onor, ML ;

Saina, M ;

Maso, E .

CURRENT MEDICAL RESEARCH AND OPINION, 2004, 20 (11) :1747-1752

[2]

Ales Z., 2010, MOLECULES, V15, P6035

[3] Neuronal nicotinic receptors: A perspective on two decades of drug discovery research [J].

Arneric, Stephen P. ;

Holladay, Mark ;

Williams, Michael .

BIOCHEMICAL PHARMACOLOGY, 2007, 74 (08) :1092-1101

[4] Geranylated flavanones from the secretion on the surface of the immature fruits of Paulownia tomentosa [J].

Asai, Teigo ;

Hara, Noriyuki ;

Kobayashi, Sawa ;

Kohshima, Shiro ;

Fujimoto, Yoshinori .

PHYTOCHEMISTRY, 2008, 69 (05) :1234-1241

[5] Nicotinic Acetylcholine Receptor Signalling: Roles in Alzheimer's Disease and Amyloid Neuroprotection [J].

Buckingham, Steven D. ;

Jones, Andrew K. ;

Brown, Laurence A. ;

Sattelle, David B. .

PHARMACOLOGICAL REVIEWS, 2009, 61 (01) :39-61

[6] TOMENTOSIDE AND 7-HYDROXYTOMENTOSIDE, 2 IRIDOID GLUCOSIDES FROM PAULOWNIA-TOMENTOSA [J].

DAMTOFT, S ;

JENSEN, SR .

PHYTOCHEMISTRY, 1993, 34 (06) :1636-1638

[7] A NEW AND RAPID COLORIMETRIC DETERMINATION OF ACETYLCHOLINESTERASE ACTIVITY [J].

ELLMAN, GL ;

COURTNEY, KD ;

ANDRES, V ;

FEATHERSTONE, RM .

BIOCHEMICAL PHARMACOLOGY, 1961, 7 (02) :88-&

[8] The influence of the support nature on the kinetics parameters, inhibition constants and reactivation of immobilized acetylcholinesterase [J].

Gabrovska, Katya ;

Marinov, Ivaylo ;

Godjevargova, Tzonka ;

Portaccio, Marianna ;

Lepore, Maria ;

Grano, Valentina ;

Diano, Nadia ;

Mita, Damiano Gustavo .

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2008, 43 (04) :339-345

[9] Slow-binding inhibition of soybean lipoxygenase-1 by dodecyl gallate [J].

Ha, Tae Joung ;

Kubo, Isao .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2007, 55 (02) :446-451

[10] Kinetics of human serum butyrylcholinesterase inhibition by a novel experimental alzheimer therapeutic, dihydrobenzodioxepine cymserine [J].

Kamal, Mohammad A. ;

Klein, Peter ;

Luo, Weiming ;

Li, Yazhou ;

Holloway, Harold W. ;

Tweedie, David ;

Greig, Nigel H. .

NEUROCHEMICAL RESEARCH, 2008, 33 (05) :745-753

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