Heterocyclic Scaffolds for the Treatment of Alzheimer's Disease

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Abstract

Background: The treatment and diagnosis of Alzheimer’s Disease (AD) are twoof the most urgent goals for research around the world. The cognitive decline is generallyassociated with the elevated levels of extracellular senile plaques, intracellular neurofibril-lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrainneurons transmission. Even if several key targets are under fervent investigation in the cureof AD, till now, the only approved therapeutic strategy is the treatment of symptoms byusing cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase(AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of acetylcho-line levels, but also play an pivotal role in A -aggregation during the early stages of senileplaque formation. On the other hand the difficult management of AD is also related to ef-fective diagnostic methods and efficient assays for the study of pathological features. Insuch complex a wide framework, heterocyclic molecules are essential backbone to buildnew and selective drugs as well as diagnostic probes. Methods: The goal of this review is to examine a selected sample of relevant applications of five- and six-membered heterocycles in AD's therapeutic approaches. Results: Concerning the research on AD, the contribution of heterocyclic compounds is huge and here we report some representative examples. The review is organized in two main sections focused on five and six-membered het- erocycles. The analyzed cases have been classified on the base of the structural features of molecules, taking into account the progressive increase in heteroatoms number. Conclusion: The discovery of an effective therapy or a diagnostic protocol for AD is still far, but consistent improvements are underway and contribution of heterocyc- lic compounds will be consistent and hopefully determinant.
Lingua originaleEnglish
pagine (da-a)3971-3995
Numero di pagine25
RivistaCURRENT PHARMACEUTICAL DESIGN
Volume22(26)
Stato di pubblicazionePublished - 2016

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Alzheimer Disease
Heterocyclic Compounds
Neurofibrils
Butyrylcholinesterase
Cholinesterase Inhibitors
Amyloid Plaques
Acetylcholinesterase
Research
Cholinergic Agents
Therapeutics
Enzymes
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

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title = "Heterocyclic Scaffolds for the Treatment of Alzheimer's Disease",
abstract = "Background: The treatment and diagnosis of Alzheimer’s Disease (AD) are twoof the most urgent goals for research around the world. The cognitive decline is generallyassociated with the elevated levels of extracellular senile plaques, intracellular neurofibril-lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrainneurons transmission. Even if several key targets are under fervent investigation in the cureof AD, till now, the only approved therapeutic strategy is the treatment of symptoms byusing cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase(AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of acetylcho-line levels, but also play an pivotal role in A -aggregation during the early stages of senileplaque formation. On the other hand the difficult management of AD is also related to ef-fective diagnostic methods and efficient assays for the study of pathological features. Insuch complex a wide framework, heterocyclic molecules are essential backbone to buildnew and selective drugs as well as diagnostic probes. Methods: The goal of this review is to examine a selected sample of relevant applications of five- and six-membered heterocycles in AD's therapeutic approaches. Results: Concerning the research on AD, the contribution of heterocyclic compounds is huge and here we report some representative examples. The review is organized in two main sections focused on five and six-membered het- erocycles. The analyzed cases have been classified on the base of the structural features of molecules, taking into account the progressive increase in heteroatoms number. Conclusion: The discovery of an effective therapy or a diagnostic protocol for AD is still far, but consistent improvements are underway and contribution of heterocyc- lic compounds will be consistent and hopefully determinant.",
author = "Riccardo Bonsignore and Antonino Lauria and Ivana Pibiri and Silvestre Buscemi and Annamaria Martorana and Andrea Pace and Carla Gentile and {Palumbo Piccionello}, Antonio and Valentina Giacalone and Andrea Pace and Piccionello, {Antonio Palumbo}",
year = "2016",
language = "English",
volume = "22(26)",
pages = "3971--3995",
journal = "CURRENT PHARMACEUTICAL DESIGN",
issn = "1381-6128",

}

TY - JOUR

T1 - Heterocyclic Scaffolds for the Treatment of Alzheimer's Disease

AU - Bonsignore, Riccardo

AU - Lauria, Antonino

AU - Pibiri, Ivana

AU - Buscemi, Silvestre

AU - Martorana, Annamaria

AU - Pace, Andrea

AU - Gentile, Carla

AU - Palumbo Piccionello, Antonio

AU - Giacalone, Valentina

AU - Pace, Andrea

AU - Piccionello, Antonio Palumbo

PY - 2016

Y1 - 2016

N2 - Background: The treatment and diagnosis of Alzheimer’s Disease (AD) are twoof the most urgent goals for research around the world. The cognitive decline is generallyassociated with the elevated levels of extracellular senile plaques, intracellular neurofibril-lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrainneurons transmission. Even if several key targets are under fervent investigation in the cureof AD, till now, the only approved therapeutic strategy is the treatment of symptoms byusing cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase(AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of acetylcho-line levels, but also play an pivotal role in A -aggregation during the early stages of senileplaque formation. On the other hand the difficult management of AD is also related to ef-fective diagnostic methods and efficient assays for the study of pathological features. Insuch complex a wide framework, heterocyclic molecules are essential backbone to buildnew and selective drugs as well as diagnostic probes. Methods: The goal of this review is to examine a selected sample of relevant applications of five- and six-membered heterocycles in AD's therapeutic approaches. Results: Concerning the research on AD, the contribution of heterocyclic compounds is huge and here we report some representative examples. The review is organized in two main sections focused on five and six-membered het- erocycles. The analyzed cases have been classified on the base of the structural features of molecules, taking into account the progressive increase in heteroatoms number. Conclusion: The discovery of an effective therapy or a diagnostic protocol for AD is still far, but consistent improvements are underway and contribution of heterocyc- lic compounds will be consistent and hopefully determinant.

AB - Background: The treatment and diagnosis of Alzheimer’s Disease (AD) are twoof the most urgent goals for research around the world. The cognitive decline is generallyassociated with the elevated levels of extracellular senile plaques, intracellular neurofibril-lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrainneurons transmission. Even if several key targets are under fervent investigation in the cureof AD, till now, the only approved therapeutic strategy is the treatment of symptoms byusing cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase(AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of acetylcho-line levels, but also play an pivotal role in A -aggregation during the early stages of senileplaque formation. On the other hand the difficult management of AD is also related to ef-fective diagnostic methods and efficient assays for the study of pathological features. Insuch complex a wide framework, heterocyclic molecules are essential backbone to buildnew and selective drugs as well as diagnostic probes. Methods: The goal of this review is to examine a selected sample of relevant applications of five- and six-membered heterocycles in AD's therapeutic approaches. Results: Concerning the research on AD, the contribution of heterocyclic compounds is huge and here we report some representative examples. The review is organized in two main sections focused on five and six-membered het- erocycles. The analyzed cases have been classified on the base of the structural features of molecules, taking into account the progressive increase in heteroatoms number. Conclusion: The discovery of an effective therapy or a diagnostic protocol for AD is still far, but consistent improvements are underway and contribution of heterocyc- lic compounds will be consistent and hopefully determinant.

UR - http://hdl.handle.net/10447/207012

M3 - Article

VL - 22(26)

SP - 3971

EP - 3995

JO - CURRENT PHARMACEUTICAL DESIGN

JF - CURRENT PHARMACEUTICAL DESIGN

SN - 1381-6128

ER -