Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease

Hamuľaková, Slávka; Janovec, Ladislav; Hrabinová, Martina; Kristián, Pavol; Kuča, Kamil; Baňasová, Mária; Imrich, Ján

doi:10.1016/j.ejmech.2012.06.051

Cited by 29 publications

(14 citation statements)

References 43 publications

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“…In another study, Hamulakova et al () described the synthesis of two series of novel homo‐tacrine cholinesterase inhibitors, compounds 8a–d and 9a–d . Compound 10 has an ethyl‐piperazine spacer between the tacrine homodimer and the corresponding secondary amines (Figure ).…”

Section: Synthetic Modes Of Tacrine Derivativesmentioning

confidence: 99%

“…Chemical structure of tacrine derivatives 8–a–d and 9a–d and tacrine homodimer 10 (Hamulakova et al, )…”

Section: Synthetic Modes Of Tacrine Derivativesmentioning

confidence: 99%

“…The same research team also described a novel series of tacrine derivatives, compounds 8a–d and 9a–d , with an ethyl‐piperazine spacer linked with corresponding secondary amines, the novel tacrine homodimer 10 (Hamulakova et al, ), and the series of homodimeric tacrine–tacrine thioureas, derivatives 13a–c , all of which exhibited modest AChE and BChE inhibitory activity with IC 50 values in the low nanomolar range (Hamulakova, Imrich, Janovec, et al, ). A further study from this group also described the synthesis of another series of novel tacrine derivatives and tacrine/coumarine heterodimers, derivatives 14a–c , 15a–c and 16a–c , which were found to be potent AChE and BChE inhibitors with IC 50 values in the micromolar range.…”

Section: Biological Activity Of Tacrine Congenersmentioning

confidence: 99%

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Multifunctional properties of novel tacrine congeners: cholinesterase inhibition and cytotoxic activity

Sabolová¹,

Kristián

Kožurková

2018

J of Applied Toxicology

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This review describes the synthesis of a wide range of novel tetrahydroacridine derivatives (tiocyanates, selenocyanates, ureas, selenoureas, thioureas, isothioureas, disulfides, diselenides and several tacrine homo- and hetro-hybrids). These tacrine congeners exhibit significant anticholinesterase and cytotoxic properties and may therefore be of considerable potential for the development of new drugs for the treatment of Alzheimer's disease.

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Section: Synthetic Modes Of Tacrine Derivativesmentioning

confidence: 99%

“…Chemical structure of tacrine derivatives 8–a–d and 9a–d and tacrine homodimer 10 (Hamulakova et al, )…”

Section: Synthetic Modes Of Tacrine Derivativesmentioning

confidence: 99%

Section: Biological Activity Of Tacrine Congenersmentioning

confidence: 99%

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Multifunctional properties of novel tacrine congeners: cholinesterase inhibition and cytotoxic activity

Sabolová¹,

Kristián

Kožurková

2018

J of Applied Toxicology

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“…On this basis, the aim of this study was to design novel drugs as inhibitors of two potential targets, SSAO/VAP-1 and AChE, involved in various multifactorial diseases such as AD. The known structurally diverse inhibitors of SSAO/VAP-1 [8][9][10][11][12][13][14][15][16] and AChE were taken from the literature [24][25][26][27][28][29][30][31][32]. These inhibitors were deconstructed into small fragments according to fragmentation rules.…”

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confidence: 99%

Multitarget fragment‐based design of novel inhibitors for AChE and SSAO/VAP‐1 enzymes

Gharaghani

Khayamian

Ebrahimi

2013

Journal of Chemometrics

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In Alzheimer's disease, increased human semicarbazide‐sensitive amine oxidase/vascular adhesion protein‐1 (SSAO/VAP‐1) expression has been found to colocalize with abnormal amyloid deposition. In addition, inhibition of acetylcholinesterase in Alzheimer's disease treatment should allow the lowered levels of acetylcholine in the synapses a chance to induce a signal in the downstream nerve. We designed inhibitors that interacted with both enzymes. The known inhibitors of acetylcholinesterase and SSAO/VAP‐1 were deconstructed into small fragments. Each fragment was docked to both enzymes, and the scoring function together with the ‘rule of three’ was used for fragment selection. The active fragments were combined with each other and resulted in 121 compounds. The docked pose of these compounds showed that seven compounds interacted in the binding site of both enzymes. Absorption, distribution, metabolism, elimination, and toxicity properties of these compounds were then calculated. The results showed that four of these inhibitors need to be synthesized for further experimental evaluation. Copyright © 2013 John Wiley & Sons, Ltd.

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“…A series of novel monotacrine, tacrine-tacrine, tacrine-acridine, tacrine-coumarin, acridine-coumarin and tacrine-quinoline ligands were designed, synthesized, and biologically evaluated as inhibitors of both AChE and butyrylcholinesterase (BChE) [1–3]. Among of monotacrine ligands, compound in which tacrine is connected to an (benzylpiperazinyl)etyl unit exhibited excellent inhibitory activity against hBChE (IC 50 =0.4 nM) [2].…”

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2018

Interdisciplinary Toxicology

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Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease

Cited by 29 publications

References 43 publications

Multifunctional properties of novel tacrine congeners: cholinesterase inhibition and cytotoxic activity

Multifunctional properties of novel tacrine congeners: cholinesterase inhibition and cytotoxic activity

Multitarget fragment‐based design of novel inhibitors for AChE and SSAO/VAP‐1 enzymes

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