Preparation of 7‐Methoxy Tacrine Dimer Analogs and Their <i>In vitro/In silico</i> Evaluation as Potential Cholinesterase Inhibitors

Lee, Sang Kwang; Park, Min Kyun; Jhang, Ho Eun; Yi, Jinju; Nahm, Keepyong; Cho, Dae Won; Sup, Choon; Musílek, Kamil; Horova, Anna; Korábečný, Jan; Doležal, Rafael; Jun, Daniel; Kuča, Kamil

doi:10.1002/bkcs.10317

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…The results of previous studies have shown that both tacrine and 7-MEOTA are capable of binding to the peripheral anionic site (PAS) as well as to the catalytic anionic site (CAS) of AChE, depending on the structural features of the second attached moiety [22]. The length of the alkyl chain plays an important role in providing proper contact to both crucial parts of the enzyme as shown previously in many studies [23,24]. This might be different for AChE and BChE due to their conformational diversity [25].…”

Section: Introductionmentioning

confidence: 90%

7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment

et al. 2015

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Alzheimer's disease (AD) is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient's death. Despite the fact that novel pharmacological approaches endeavoring to block the neurodegenerative process are still emerging, none of them have reached use in clinical practice yet. Thus, palliative treatment represented by acetylcholinesterase inhibitors (AChEIs) and memantine are still the only therapeutics used. Following the multi-target directed ligands (MTDLs) strategy, herein we describe the synthesis, biological evaluation and docking studies for novel 7-methoxytacrine-p-anisidine hybrids designed to purposely target both cholinesterases and the amyloid cascade. Indeed, the novel derivatives proved to be effective non-specific cholinesterase inhibitors showing non-competitive AChE inhibition patterns. This compounds' behavior was confirmed in the subsequent molecular modeling studies.

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Section: Introductionmentioning

confidence: 90%

7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment

et al. 2015

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“…Compound 1 was synthesized using the procedure previously reported in the literature, 22 using a solution of triethylene glycol in dichloromethane at 0 o C with p-toluenesulfonyl chloride in the presence of triethylamine as base. Compound 2 was synthesized using a common procedure reported in the literature 23 for the synthesis of iodoalkanes using sodium iodide in acetone at reflux.…”

Section: Synthesismentioning

confidence: 99%

When Serendipity Knocks on the Door: Synthesis and Physicochemical Characterization of 7-Chloro-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-one

Carmona‐Vargas

Ellena

D’Vries

et al. 2019

J. Braz. Chem. Soc.

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Herein, we present the serendipitous obtaining of 7-chloro-2,3-dihydro-5H-thiazolo [3,2-a]pyrimidin-5-one in 40% yield by using POCl 3 and a thiobarbituric acid derivative. The thiazolopyrimidine derivative was characterized by 1 H nuclear magnetic resonance (NMR), UV-Vis, and Fourier transform infrared (FTIR) spectroscopy. Additionally, the structure was confirmed by single crystal X-ray diffraction, where it was found that the compound crystallizes in the P-1 triclinic space group with two conformeric molecules of 7-chloro-2,3-dihydro-5H-thiazolo [3,2-a]pyrimidin-5-one by asymmetric unit. Also, from the structural data was studied the supramolecular interactions using Hirshfeld surface analysis and 2D fingerprint plots.

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“…Tacrine was the first AChE inhibitor to be approved by the US Food and Drug Administration for clinical use but the drug had a number of problematic side effects, primarily the elevation of toxicity of liver enzymes in AD patients, which was dose-dependent and reversible after a reduction in dosage or complete withdrawal (Unzeta et al, 2016). Over the years, a substantial number of tacrine derivatives and its analogues have been synthesized in an attempt to limit the side effects of the agent (Horak et al, 2017;Hroudová, Singh, Fišar, & Ghosh, 2016;Kračmárová, Drtinová, & Pohanka, 2015;Lee et al, 2015;Reddy et al, 2017;Teponnou, Joubert, & Malan, 2017). 2,3,tetrahydro-acridinamine hydrochlorides using the cholinergic drug tacrine as a base.…”

Section: Tacrine Derivatives As Cholinesterase Inhibitorsmentioning

confidence: 99%

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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Preparation of 7‐Methoxy Tacrine Dimer Analogs and Their In vitro/In silico Evaluation as Potential Cholinesterase Inhibitors

Cited by 10 publications

References 38 publications

7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment

7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment

When Serendipity Knocks on the Door: Synthesis and Physicochemical Characterization of 7-Chloro-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-one

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

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