Cholinesterase inhibitors as Alzheimer's therapeutics

被引:577
作者
Sharma, Kamlesh [1 ]
机构
[1] Shree Guru Gobind Singh Tricentenary Univ, Fac Phys Sci, Dept Chem, Gurgaon Badli Rd Chandu, Gurugram 122505, Haryana, India
关键词
Alzheimer's; dementia; cholinesterase; inhibitor; multi-target; BETA-AMYLOID AGGREGATION; PLACEBO-CONTROLLED TRIAL; ACETYLCHOLINESTERASE INHIBITORS; BIOLOGICAL EVALUATION; DOUBLE-BLIND; DISEASE; DONEPEZIL; TACRINE; HYBRIDS; DESIGN;
D O I
10.3892/mmr.2019.10374
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Alzheimer's disease (AD) is one of the most common forms of dementia. AD is a chronic syndrome of the central nervous system that causes a decline in cognitive function and language ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed for the treatment of AD, including naturally-derived inhibitors, synthetic analogues and hybrids. Currently, the available drugs for AD are predominantly cholinesterase inhibitors. However, the efficacy of these drugs is limited as they may cause adverse side effects and are not able to completely arrest the progression of the disease. Since AD is multifactorial disease, dual and multi-target inhibitors have been developed. The clinical applications and the limitations of the inhibitors used to treat AD are discussed in the present review. Additionally, this review presents the current status and future directions for the development of novel drugs with reduced toxicity and preserved pharmacological activity.
引用
收藏
页码:1479 / 1487
页数:9
相关论文
共 95 条
[1]   Design, synthesis and evaluation of novel 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-2-indenyl-3,4-substituted phenyl methanone analogues [J].
Ali, Mohamed Ashraf ;
Yar, Mohammad Shahar ;
Hasan, Mohamed Zaheen ;
Ahsan, Mohamed Jawed ;
Pandian, Suresh .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (17) :5075-5077
[2]   Early investigational drugs targeting tau protein for the treatment of Alzheimer's disease [J].
Anand, Keshav ;
Sabbagh, Marwan .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2015, 24 (10) :1355-1360
[3]  
Azam F, 2014, DRUG DES DEV THER, V8, P2045, DOI 10.2147/DDDT.S67778
[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]   THE CHOLINERGIC HYPOTHESIS OF GERIATRIC MEMORY DYSFUNCTION [J].
BARTUS, RT ;
DEAN, RL ;
BEER, B ;
LIPPA, AS .
SCIENCE, 1982, 217 (4558) :408-417
[6]   (-)- Phenserine and Inhibiting Pre-Programmed Cell Death: In Pursuit of a Novel Intervention for Alzheimer's Disease [J].
Becker, Robert E. ;
Greig, Nigel H. ;
Lahiri, Debomoy K. ;
Bledsoe, Joseph ;
Majercik, Sarah ;
Ballard, Clive ;
Aarsland, Dag ;
Schneider, Lon S. ;
Flanagan, Douglas ;
Govindarajan, Ramprakash ;
Sano, Mary ;
Ferrucci, Luigi ;
Kapogiannis, Dimitrios .
CURRENT ALZHEIMER RESEARCH, 2018, 15 (09) :883-891
[7]   Targeting Acetylcholinesterase: Identification of Chemical Leads by High Throughput Screening, Structure Determination and Molecular Modeling [J].
Berg, Lotta ;
Andersson, C. David ;
Artursson, Elisabet ;
Hornberg, Andreas ;
Tunemalm, Anna-Karin ;
Linusson, Anna ;
Ekstrom, Fredrik .
PLOS ONE, 2011, 6 (11)
[8]   Design, synthesis, cholinesterase inhibition and molecular modelling study of novel tacrine hybrids with carbohydrate derivatives [J].
Bizarro Lopes, Joao Paulo ;
Silva, Luana ;
Franarin, Gabriela da Costa ;
Ceschi, Marco Antonio ;
Ludtke, Diogo Seibert ;
Dantas, Rafael Ferreira ;
Cardoso de Salles, Cristiane Martins ;
Silva-, Floriano Paes, Jr. ;
Senger, Mario Roberto ;
Guedes, Isabella Alvim ;
Dardenne, Laurent Emmanuel .
BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (20) :5566-5577
[9]   New tacrine-huperzine A hybrids (huprines):: Highly potent tight-binding acetylcholinesterase inhibitors of interest for the treatment of Alzheimer's disease [J].
Camps, P ;
El Achab, R ;
Morral, J ;
Muñoz-Torrero, D ;
Badia, A ;
Baños, JE ;
Vivas, NM ;
Barril, X ;
Orozco, M ;
Luque, FJ .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (24) :4657-4666
[10]   Novel donepezil-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation [J].
Camps, Pelayo ;
Formosa, Xavier ;
Galdeano, Carles ;
Gomez, Tania ;
Munoz-Torrero, Diego ;
Scarpellini, Michele ;
Viayna, Elisabet ;
Badia, Albert ;
Clos, M. Victoria ;
Camins, Antoni ;
Pallas, Merce ;
Bartolini, Manuela ;
Mancini, Francesca ;
Andrisano, Vincenza ;
Estelrich, Joan ;
Lizondo, Monica ;
Bidon-Chanal, Axel ;
Luque, F. Javier .
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (12) :3588-3598