Synthesis and biological evaluation of new pyrazolone Schiff bases as monoamine oxidase and cholinesterase inhibitors

Tok, Fatih; Koçyığıt‐Kaymakcioğlu, Bedia; Sağlık, Begüm Nurpelin; Levent, Serkan; Özkay, Yusuf; Kaplancıklı, Zafer Asım

doi:10.1016/j.bioorg.2018.11.016

Cited by 65 publications

(67 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on the structure of leading compound edaravone, Tok and co-workers [75] synthesized a cluster of analogues and investigated the potential anti-Alzheimer activity. Among the analogues, compounds 108 and 109 ( Fig.…”

Section: Anti-alzheimer's Agentsmentioning

confidence: 99%

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Zhao

Dai

et al. 2020

European Journal of Medicinal Chemistry

130

View full text Add to dashboard Cite

a b s t r a c tThe pyrazolone structural motif is a critical element of drugs aimed at different biological end-points. Medicinal chemistry researches have synthesized drug-like pyrazolone candidates with several medicinal features including antimicrobial, antitumor, CNS (central nervous system) effect, anti-inflammatory activities and so on. Meanwhile, SAR (Structure-Activity Relationship) investigations have drawn attentions among medicinal chemists, along with a plenty of analogues have been derived for multiple targets. In this review, we comprehensively summarize the biological activity and SAR for pyrazolone analogues, wishing to give an overall retrospect and prospect on the pyrazolone derivatives.

show abstract

Section: Anti-alzheimer's Agentsmentioning

confidence: 99%

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Zhao

Dai

et al. 2020

European Journal of Medicinal Chemistry

130

View full text Add to dashboard Cite

show abstract

“…The reagents and materials used in the enzyme inhibition assay were supplied commercially from Sigma-Aldrich (St. Louis, MO, USA) and Fluka (Steinheim, Germany). The cholinesterase enzyme inhibition procedure was applied as previously reported in our research papers [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, a substrate (ATC) was used at various concentrations (600, 300, 150, 75, 37.5, and 18.75 µM). The enzyme kinetics assay was carried out as in our previous publications [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Lineweaver–Burk plots were formed using Microsoft Office Excel 2013.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Design, Synthesis, and Structure–Activity Relationships of Thiazole Analogs as Anticholinesterase Agents for Alzheimer’s Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

Dementia is a neurological condition commonly correlated with Alzheimer’s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a–2l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 ± 0.003, 0.056 ± 0.002, 0.147 ± 0.006, 0.040 ± 0.001, 0.031 ± 0.001, 0.028 ± 0.001, and 0.138 ± 0.005 µM, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 ± 0.001 µM, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.

show abstract

“…MAO inhibition assay including fluorometric measurement of Ampliflu Red (10‐acetyl‐3,7‐dihydroxyphenoxazine) was performed. Inhibitory activity of synthesized compounds ( 4a ‐ 4k ) against MAO A and MAO B enzymes was measured as reported earlier …”

Section: Methodsmentioning

confidence: 99%

Synthesis and evaluation of new pyrazoline‐thiazole derivatives as monoamine oxidase inhibitors

Çevik

Osmaniye

Sağlık

et al. 2019

Journal of Heterocyclic Chem

Self Cite

View full text Add to dashboard Cite

A novel series of 1,3,5‐trisubstituted‐2‐pyrazoline derivatives (4a‐4k) was synthesized and their chemical structures characterized by 1H NMR, 13C NMR, and mass spectroscopy. These compounds were evaluated as inhibitors for of type A and type B monoamine oxidase (MAO) enzymes. The most common inhibitors of MAO enzymes used to treat depression and anxiety such as selegiline and moclobemide drugs were used as reference agents. A result of biological evaluation of these compounds revealed compounds 4c, 4d, and 4ı as potent and selective MAO A inhibitors. The most active compound 4ı, which is 2,4‐dimethoxy at phenyl ring, showed strong inhibitory activity at MAO A (IC50 of 0.0445 ± 0.0018μM). Furthermore, compounds 4c and 4d showed significant inhibition profile on MAO A with the IC50 values 0.1423 ± 0.0051μM and 0.2148 ± 0.0067μM, respectively.

show abstract

Synthesis and biological evaluation of new pyrazolone Schiff bases as monoamine oxidase and cholinesterase inhibitors

Cited by 65 publications

References 32 publications

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Design, Synthesis, and Structure–Activity Relationships of Thiazole Analogs as Anticholinesterase Agents for Alzheimer’s Disease

Synthesis and evaluation of new pyrazoline‐thiazole derivatives as monoamine oxidase inhibitors

Contact Info

Product

Resources

About