Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors

Kálai, Tamás; Altman, Robin; Maezawa, Izumi; Balog, Mária; Morisseau, Christophe; Petrlová, Jitka; Hammock, Bruce D.; Jin, Lee Way; Trudell, James R.; Voss, John C.; Hideg, Kálmán

doi:10.1016/j.ejmech.2014.03.026

Cited by 12 publications

(7 citation statements)

References 31 publications

(33 reference statements)

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“…With these concepts in mind, Kalai et al. 113 combined nitroxide and/or nitroxide precursors (amines and hydroxylamines) with tacrine via methylene or piperazine space. The synthetic compounds were tested for their hydroxyl radical and peroxyl radical-scavenging ability, acetylcholinesterase inhibitor activity, and protection against Aβ-induced cytotoxicity.…”

Section: Design Of Multitarget-directed Tacrine Derivativesmentioning

confidence: 99%

Novel multitarget-directed tacrine derivatives as potential candidates for the treatment of Alzheimer’s disease

Dai

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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Alzheimer’s disease (AD) is a neurodegenerative disorder, which is complex and progressive; it has not only threatened the health of elderly people, but also burdened the whole social medical and health system. The available therapy for AD is limited and the efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the design and development of efficacious and safe anti-AD agents has become a hotspot in the field of pharmaceutical research. Due to the multifactorial etiology of AD, the multitarget-directed ligands (MTDLs) approach is promising in search for new drugs for AD. Tacrine, which is the first acetylcholinesterase (AChE) inhibitor, has been selected as the ideal active fragment because of its simple structure, clear activity, and its superiority in the structural modification, thus it could be introduced into the overall molecular skeletons of the multi-target-directed anti-AD agents. In this review, we have summarized the recent advances (2012 to the present) in the chemical modification of tacrine, which could provide the reference for the further study of novel multi-target-directed tacrine derivatives to treat AD.

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Section: Design Of Multitarget-directed Tacrine Derivativesmentioning

confidence: 99%

Novel multitarget-directed tacrine derivatives as potential candidates for the treatment of Alzheimer’s disease

Dai

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…The tacrine analog 32 ( Figure 8) having a nitroxide substituent at 9-amino group via piperazine linker displayed very good AChE inhibitory activity (IC 50 <5000 nM) in bovine erythrocyte and efficient protection against Aβ-induced cytotoxicity (PC 50 < 2000 nM) in MC65 cells [67]. The tacrine-(β-carboline) heterodimers [68] (33 of Figure 8) were evaluated for their role as multifunctional cholinesterase inhibitors.…”

Section: Tacrine Analogsmentioning

confidence: 99%

The Structural Hybrids of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease: A Review

Saxena¹

2019

AND

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Alzheimer's Disease (AD) is characterized by the loss of memory and learning ability in elderly patients affecting large population worldwide. The enzyme Acetylcholinesterase (AChE), (E.C.3.1.1.7) plays a major role in the hydrolysis of the released neurotransmitter acetylcholine. Most of the clinically used drugs to treat AD are Acetylcholinesterase Inhibitors (AChEIs). These drugs can provide symptomatic benefits only and suffer with loss of therapeutic potential with time. Therefore, there is an urgent need of novel cholinesterase inhibitors with wider therapeutic window for the treatment of AD. The strategies targeting the AChE enzyme along with other target(s) like Butyrylcholinesterase (BChE), amyloid-β (Aβ), β-secretase-1 (BACE), metals (Cu 2+ , Zn 2+ , or Fe 2+), antioxidant properties and free radical scavenging capacity have been mainly focused in the last five years. A number of hybrid molecules incorporating sub-structures with the desired well-established pharmacological profile into a single scaffold have been investigated. The main sub structures used in developing these molecules are derived from diverse chemical classes such as acridine, quinoline, carbamates, huperzine and other heterocyclic analogs. It has been followed by optimization of activity through structural modifications of the prototype molecules for developing the Structure Activity Relationship (SAR). This has led to the development of novel molecules with desired AChE inhibitory activity along with other desirable pharmacological properties. This review summarizes the current therapeutic strategies for the development of these AChEI in the last seven years.

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“…8 Usually, the starting point for the design of such compounds is the structure of a known AChE inhibitor, which is linked to an antioxidant pharmacophoric moiety, [11][12][13][14][15][16][17][18] e.g. phenolics and polyphenolics derived fragments.…”

Section: Introductionmentioning

confidence: 99%

Shogaol–huprine hybrids: Dual antioxidant and anticholinesterase agents with β-amyloid and tau anti-aggregating properties

Pérez-Areales

Pietro

Espargaró³

et al. 2014

Bioorganic & Medicinal Chemistry

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Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors

Cited by 12 publications

References 31 publications

Novel multitarget-directed tacrine derivatives as potential candidates for the treatment of Alzheimer’s disease

Novel multitarget-directed tacrine derivatives as potential candidates for the treatment of Alzheimer’s disease

The Structural Hybrids of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer’s Disease: A Review

Shogaol–huprine hybrids: Dual antioxidant and anticholinesterase agents with β-amyloid and tau anti-aggregating properties

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