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 two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibril- lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using 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 senile plaque 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. In such complex a wide framework, heterocyclic molecules are essential backbone to build new 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 two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibril- lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using 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 senile plaque 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. In such complex a wide framework, heterocyclic molecules are essential backbone to build new 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 = "Silvestre Buscemi and Antonino Lauria and Andrea Pace and Ivana Pibiri and Annamaria Martorana and Carla Gentile and {Palumbo Piccionello}, Antonio and Riccardo Bonsignore and Valentina Giacalone and Piccionello, {Antonio Palumbo} and Andrea Pace",
year = "2016",
language = "English",
volume = "22(26)",
pages = "3971--3995",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",

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TY - JOUR

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

AU - Buscemi, Silvestre

AU - Lauria, Antonino

AU - Pace, Andrea

AU - Pibiri, Ivana

AU - Martorana, Annamaria

AU - Gentile, Carla

AU - Palumbo Piccionello, Antonio

AU - Bonsignore, Riccardo

AU - Giacalone, Valentina

AU - Piccionello, Antonio Palumbo

AU - Pace, Andrea

PY - 2016

Y1 - 2016

N2 - Background: The treatment and diagnosis of Alzheimer’s Disease (AD) are two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibril- lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using 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 senile plaque 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. In such complex a wide framework, heterocyclic molecules are essential backbone to build new 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 two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibril- lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using 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 senile plaque 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. In such complex a wide framework, heterocyclic molecules are essential backbone to build new 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 -