(+)-Arisugacin A-Computational evidence of a dual binding site covalent inhibitor of acetylcholinesterase

被引：12

作者：

Al-Rashid, Ziyad F. ^{[1
]}

Hsung, Richard P. ^{[2
,3
]}

机构：

[1] Alchem Res LLC, Bethlehem, PA 18018 USA

[2] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA

[3] Univ Wisconsin, Dept Chem, Madison, WI 53705 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 09期

关键词：

Arisugacin A; Acetylcholinesterase inhibitor; Alzheimer's disease; Dual binding site; Covalent inhibitor; CATION-PI INTERACTIONS; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; CHOLINESTERASE-INHIBITORS; CEREBROSPINAL-FLUID; HUPERZINE-A; DERIVATIVES; ARISUGACIN; PATHOGENESIS; DEMENTIA;

D O I：

10.1016/j.bmcl.2010.12.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A computation docking study of the highly potent, non-nitrogen containing, acetylcholinesterase inhibitor (+)-arisugacin A is presented. The model suggests that (+)-arisugacin A is a dual binding site covalent inhibitor of AChE. These findings are examined in the context of Alzheimer's disease-modifying therapeutic design. (+)-Arisugacin A's revealed mode of action is unique, and may serve as a basis for the development of AD therapeutics capable of treating the symptomatic aspects of AD, while being neuroprotective with long term efficacy. (C) 2010 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2687 / 2691

页数：5

相关论文

共 82 条

[1] Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils [J].

Alvarez, A ;

Opazo, C ;

Alarcon, R ;

Garrido, J ;

Inestrosa, NC .

JOURNAL OF MOLECULAR BIOLOGY, 1997, 272 (03) :348-361

[2]

Alzheimer A., 1907, GESAMTE PSYCHIAT, V64, P1264

[3] Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease [J].

Bai, DL ;

Tang, XC ;

He, XC .

CURRENT MEDICINAL CHEMISTRY, 2000, 7 (03) :355-374

[4] Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine [J].

Bar-On, P ;

Millard, CB ;

Harel, M ;

Dvir, H ;

Enz, A ;

Sussman, JL ;

Silman, I .

BIOCHEMISTRY, 2002, 41 (11) :3555-3564

[5] Cholinesterase inhibitors:: Xanthostigmine derivatives blocking the acetylcholinesterase-induced β-amyloid aggregation [J].

Belluti, F ;

Rampa, A ;

Piazzi, L ;

Bisi, A ;

Gobbi, S ;

Bartolini, M ;

Andrisano, V ;

Cavalli, A ;

Recanatini, M ;

Valenti, P .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (13) :4444-4456

[6] Multi-target-directed drug design strategy: From a dual binding site acetylcholinesterase inhibitor to a trifunctional compound against Alzheimer's disease [J].

Bolognesi, Maria Laura ;

Cavalli, Andrea ;

Valgimigli, Luca ;

Bartolini, Manuela ;

Rosini, Michela ;

Andrisano, Vincenza ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (26) :6446-6449

[7]

Buchanan GS, 2010, CURR ORG SYNTH, V7, P363

[8] Pyrano[3,2-c]quinoline-6-Chlorotacrine Hybrids as a Novel Family of Acetylcholinesterase- and β-Amyloid-Directed Anti-Alzheimer Compounds [J].

Camps, Pelayo ;

Formosa, Xavier ;

Galdeano, Carles ;

Munoz-Torrero, Diego ;

Ramirez, Lorena ;

Gomez, Elena ;

Isambert, Nicolas ;

Lavilla, Rodolfo ;

Badia, Albert ;

Victoria Clos, M. ;

Bartolini, Manuela ;

Mancini, Francesca ;

Andrisano, Vincenza ;

Arce, Mariana P. ;

Isabel Rodriguez-Franco, M. ;

Huertas, Oscar ;

Dafni, Thomai ;

Javier Luque, F. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (17) :5365-5379

[9] Targeting beta-amyloid pathogenesis through acetylcholinesterase inhibitors [J].

Castro, Ana ;

Martinez, Ana .

CURRENT PHARMACEUTICAL DESIGN, 2006, 12 (33) :4377-4387

[10] The first enantioselective total synthesis of (-)-arisugacin A [J].

Cole, KP ;

Hsung, RP .

TETRAHEDRON LETTERS, 2002, 43 (48) :8791-8793

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