Synthesis and AChE inhibitory activity of new chiral tetrahydroacridine analogues from terpenic cyclanones

Pisoni, Diego dos Santos; Costa, Jessie Sobieski da; Gamba, Douglas; Petzhold, César Liberato; Borges, Adilson; Ceschi, Marco Antonio; Lunardi, Paula; Gonçalves, Carlos Alberto

doi:10.1016/j.ejmech.2009.10.039

Cited by 45 publications

(12 citation statements)

References 57 publications

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“…In 2004 Frideling [18] and co-workers synthesised chiral THA derivatives from 3-methylcyclohexananone, menthone, pulegone, carvone and dihydrocarvone. Pisoni [19] proposed enentioselective synthesis of THA derivatives where inhibition activity has been checked (IC50 ¼ 0.06e7.22 mM).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors

Szymański

Karpiński²,

Mikiciuk-Olasik

2011

European Journal of Medicinal Chemistry

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Section: Introductionmentioning

confidence: 99%

Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors

Szymański

Karpiński²,

Mikiciuk-Olasik

2011

European Journal of Medicinal Chemistry

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“…So far, only seven drugs Caproctamine, Donepezil, Galanthamine, Huperzine, Memantine, Rivastigmine, and Tacrine [9, 10] have been approved by the Food and Drug Administration (FDA or USFDA) for the treatment of AD. Additionally, due to numerous side effects such as hepatotoxicity, gastrointestinal disturbance, dizziness, diarrhea, vomiting, nausea, pharmacokinetic disadvantages [11], and limited number of therapeutic options for AD, there is a call to discover new more effective compounds.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation

Seniya

Khan²,

Uchadia³

2014

Biochemistry Research International

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Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.

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“…The most commonly used drug for the treatment of AD is tacrine which is recognized to have so many side effects that in most cases they lead to withdrawal of the medication. Other drugs like donepezil, rivastigmine, galanthamine, caproctamine and memantine were also used for the treatment of AD, but are known for their unfavorable effects like hepatotoxicity, gastrointestinal disturbance, dizziness, diarrhea, vomiting and nausea [ 4 , 5 , 6 ]. The key factor liley implicated in many diseases is oxidative stress caused by free radicals produced as a result of an imbalance in antioxidants produced by the cells [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, Acetylcholinesterase Inhibition, Molecular Modeling and Antioxidant Activities of Some Novel Schiff Bases Derived from 1-(2-Ketoiminoethyl)piperazines

et al. 2011

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Some novel Schiff bases derived from 1-(2-ketoiminoethyl)piperazines were synthesized and characterized by mass spectroscopy, FTIR, UV-Visible, 1H and 13C-NMR. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE), antioxidant activities, acute oral toxicity and further studied by molecular modeling techniques. The study identified the compound (DHP) to have the highest activity among the series in hAChE inhibition and DPPH assay while the compound LP revealed the highest activity in the FRAP assay. The hAChE inhibitory activity of DHP is comparable with that of propidium, a known AChE inhibitor. This high activity of DHP was checked by molecular modeling which showed that DHP could not be considered as a bivalent ligand due to its incapability to occupy the esteratic site (ES) region of the 3D crystal structure of hAChE. The antioxidant study unveiled varying results in 1,1-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. This indicates mechanistic variations of the compounds in the two assays. The potential therapeutic applications and safety of these compounds were suggested for use as human acetylcholinesterase inhibitors and antioxidants.

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Synthesis and AChE inhibitory activity of new chiral tetrahydroacridine analogues from terpenic cyclanones

Cited by 45 publications

References 57 publications

Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors

Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors

Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation

Synthesis, Characterization, Acetylcholinesterase Inhibition, Molecular Modeling and Antioxidant Activities of Some Novel Schiff Bases Derived from 1-(2-Ketoiminoethyl)piperazines

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