Quinolone–benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer Disease

Pudlo, Marc; Luzet, Vincent; Ismaïli, Lhassane; Tomassoli, Isabelle; Iutzeler, Anne; Refouvelet, Bernard

doi:10.1016/j.bmc.2014.02.046

Cited by 67 publications

(35 citation statements)

References 58 publications

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“…Again, the relationship between deleterious effects at the level of locomotor behavior and neurological impairment mediated by ChE inhibition is uncertain, considering the occurrence of a significant induction of ChE activity in ciprofloxacin‐exposed fish. Despite being a quinolone, a pharmacological group characterized as showing anticholinesterasic activity, ciprofloxacin exposure resulted in the increment of ChE in D. rerio tissues. Despite this paradoxical effect, it was not possible to devise any implication of ciprofloxacin in fish behavior, considering the generic absence of data in the literature; it is thus possible to suggest that behavioral alterations elicited by this antibiotic are a nonspecific response to a source of chemical stress.…”

Section: Discussioncontrasting

confidence: 99%

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Nogueira

Pinto

Correia

et al. 2019

Environmental Toxicology

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For several years, the scientific community has been concerned about the presence of pharmaceuticals in the wild, since these compounds may have unpredictable deleterious effects on living organisms. Two examples of widely used pharmaceuticals that are present in the environment are paracetamol and ciprofloxacin. Despite their common presence in the aquatic environment due to their poor removal by sewage treatment plants, knowledge concerning their putative toxic effects is still scarce. This work aimed to characterize the effects of paracetamol (0.005, 0.025, 0.125, 0.625, and 3.125 mg/L) and ciprofloxacin (0.005, 0.013, 0.031, 0.078, 0.195, and 0.488 μg/L) in zebrafish embryos and larvae, exposed to environmentally relevant levels, close to the real concentrations of these pharmaceuticals in surface waters and effluents. The adopted toxic end points were developmental, a behavioral parameter (total swimming time), and a biomarker‐based approach (quantification of the activities of catalase, glutathione‐S‐transferase, cholinesterases, glutathione peroxidase, and lipid peroxidation levels) combined with epigenetic analysis (immunohistochemical detection of 5‐methylcytidine). Exposure to paracetamol had effects on all of the adopted toxic end points; however, ciprofloxacin only caused effects on behavioral tests and alterations in biomarkers. It is possible to ascertain the occurrence of oxidative stress following exposure to both drugs, which was more evident regarding paracetamol, an effect that may be related to the observed epigenetic modifications.

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Section: Discussioncontrasting

confidence: 99%

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Nogueira

Pinto

Correia

et al. 2019

Environmental Toxicology

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“…The active pocket of ee AChE has two distinct binding sites: peripheral binding site (PAS) and catalytic active site (CAS). The PAS is located at the entrance of a deep and hydrophobic gorge that connects the PAS to the CAS in the bottom of the active site . The PAS comprises Trp286, Tyr124, and Tyr72.…”

Section: Resultsmentioning

confidence: 99%

“…Donepezil is the most widely employed AChE inhibitor and has been used as the prototype for several other AChE inhibitors . N ′‐Benzylidene‐2‐(4‐benzylpiperazin‐1‐yl)acylhydrazones were derived from donepezil (Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease

Fernandes

Cunha

Sakata

et al. 2017

Archiv der Pharmazie

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Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC values of 0.64-51.09 μM. The preliminary structure-activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains. Molecular dynamics studies of compound 6d showed that the interaction with the peripheral binding site of AChE was similar to donepezil, which may explain its low IC (0.64 μM). Furthermore, the drug-likeness of 6d suggests that the compound may have appropriate oral absorption and brain penetration. Compound 6d also presented antiradical activity and was not cytotoxic to LL24 cells, suggesting that this compound might be considered safe. Our findings indicate that arylsulfonylhydrazones may be a promising scaffold for the design of new drug candidates for the treatment of AD.

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“…Recently, dual binding site inhibitors (binding to both CS and PAS) have attracted lots of attention and in this field, heterocyclic compounds play crucial role. They can interact with both sites efficiently and in this regard, indolinones , huperzine A‐tacrine , quinolone–benzylpiperidine , thiazolo‐1,2,4‐triazinones , and oxoisoaporphines have shown remarkable activities.…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation, and Docking Study of Acetylcholinesterase Inhibitors: New Acridone‐1,2,4‐oxadiazole‐1,2,3‐triazole Hybrids

Mohammadi-Khanaposhtani

Mahdavi

Saeedi

et al. 2015

Chem Biol Drug Des

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In this study, novel acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity. Among various synthesized compounds, 10-((1-((3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H)-one 10b showed the most potent anti-acetylcholinesterase activity (IC50 = 11.55 μm) being as potent as rivastigmine. Also docking outcomes were in good agreement with in vitro results confirming the dual binding inhibitory activity of compound 10b.

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Quinolone–benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer Disease

Cited by 67 publications

References 58 publications

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs

Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease

Design, Synthesis, Biological Evaluation, and Docking Study of Acetylcholinesterase Inhibitors: New Acridone‐1,2,4‐oxadiazole‐1,2,3‐triazole Hybrids

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