Synthesis of new hydrazone derivatives and evaluation of their monoamine oxidase inhibitory activity

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

doi:10.1016/j.bioorg.2021.105038

Cited by 35 publications

(29 citation statements)

References 37 publications

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“…The same materials used in the MAO inhibition assay were used in this experiment. In accordance with the assay given in our previous studies, compounds 2b and 2h, which were identified as the most active selective MAO-B inhibitor candidates, were experienced at three independent concentrations of IC 50 /2, IC 50 , and 2(IC 50 ) [33][34][35][36][37][38][39]. All processes were evaluated in quadruplicate.…”

Section: Enzyme Kinetic Studiesmentioning

confidence: 73%

“…The inhibition power on MAO isoenzymes of the synthesized compounds was evaluated by using the in vitro fluorometric method declared previously by our research group [33][34][35][36][37][38][39]. The results of the first step of enzyme activity assay were given in Table 1; that of the second step was presented in Table 2.…”

Section: Mao Inhibitionmentioning

confidence: 99%

“…Compounds 2b and 2h which were found to be the most effective derivatives in the series, were included in the enzyme kinetic assay to evaluate the inhibition types of them on MAO-B enzyme. Enzyme kinetic assay was applied in the same way as previously mentioned [33][34][35][36][37][38][39]. The IC 50 /2, IC 50 , and 2(IC 50 ) were used as the concentrations of these compounds.…”

Section: Kinetic Studies Of Enzyme Inhibitionmentioning

confidence: 99%

“…According to Lineweaver-Burk plots, reversible and irreversible inhibition type constitute two general categories. Mixed-type, uncompetitive, competitive, and non-competitive inhibition types are included in the reversible inhibition [33][34][35][36][37][38][39]. As seen in the Lineweaver-Burk graphs of compounds 2b and 2h (Figures 4 and 5), the lines were intersected on the x-axis, and their slopes and y-intercepts were different.…”

Section: Kinetic Studies Of Enzyme Inhibitionmentioning

confidence: 99%

“…The in vitro MAO inhibition test was performed using the available fluorometric method, and the percentages and IC 50 values of obtained compounds were calculated as previously described by our research group [33][34][35][36][37][38][39].…”

Section: Mao-a and Mao-b Inhibition Assaymentioning

confidence: 99%

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Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

et al. 2021

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MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC50 value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The Ki values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound.

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Section: Enzyme Kinetic Studiesmentioning

confidence: 73%

Section: Mao Inhibitionmentioning

confidence: 99%

Section: Kinetic Studies Of Enzyme Inhibitionmentioning

confidence: 99%

Section: Kinetic Studies Of Enzyme Inhibitionmentioning

confidence: 99%

Section: Mao-a and Mao-b Inhibition Assaymentioning

confidence: 99%

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Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

et al. 2021

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Design, synthesis, biological activity, molecular docking, and molecular dynamics of novel benzimidazole derivatives as potential AChE/MAO‐B dual inhibitors

Osmaniye

Evren

Sağlık

et al. 2021

Archiv der Pharmazie

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To develop new acetylcholinesterase (AChE)–monoamine oxidase‐B (MAO‐B) dual inhibitors against Alzheimer's disease, the benzimidazole ring, which has a propargyl side chain with previously proven selective MAO‐B inhibitory activity, was used as the main structure. Moreover, like donepezil, it was thought that the enzyme AChE would provide π–π interactions with the peripheral anionic side in this structure. Piperazine derivatives were chosen for the cationic active site. The synthesis of the compounds was carried out in five steps. The structures of the compounds were determined using 1H‐NMR (nuclear magnetic resonance), 13C‐NMR, and high‐resolution mass spectrometry spectroscopic methods. First, the in vitro AChE, butyrylcholinesterase (BChE), MAO‐A, and MAO‐B inhibitory potentials of the obtained compounds were investigated. As a result of activity tests, compounds 5b, 5e, 5g, and 5h showed inhibitory activity against AChE; compounds 5e and 5g showed inhibitory activity against MAO‐B. None of the compounds showed inhibitory activity against BChE or MAO‐A. Compounds 5e and 5g showed dual inhibition. Among these compounds, compound 5g had inhibition potential similar to that of donepezil and selegiline. For compound 5g, further kinetic studies and Aβ‐plaque inhibitory potentials were investigated using in vitro methods. Molecular docking studies were performed using both AChE and hMAO‐B crystals to elucidate the compound's interactions with the enzyme active site. The binding modes of the compound on AChE were fully elucidated by molecular dynamics studies.

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Ultrasound‐Assisted Synthesis of Pyrazoline Derivatives as Potential Antagonists of RAGE‐Mediated Pathologies: Insights from SAR Studies and Biological Evaluations

Dascălu,

Furman,

Lancel

et al. 2024

ChemMedChem

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In the context of age‐related disorders, the receptor of advanced glycation end products (RAGE), plays a pivotal role in the pathogenesis of these conditions by triggering downstream signaling pathways associated with chronic inflammation and oxidative stress. Targeting this inflammaging phenomenon with RAGE antagonists holds promise for interventions with broad implications in healthy aging and the management of age‐related conditions. This study explores the structure‐activity relationship (SAR) of pyrazoline‐based RAGE antagonists synthesized using an ultrasound‐assisted green one‐pot two‐steps methodology. Our investigation identifies phenylurenyl‐pyrazoline 2g as a promising candidate, demonstrating superior efficiency compared to the reference antagonist Azeliragon (IC50 = 13 µM). Compound 2g exhibits potent inhibition of the AGE2‐BSA/sRAGE interaction (IC50 = 22 µM) and favorable affinity in Microscale Thermophoresis (MST) assays (Kd = 17.1 µM), along with a favorable safety profile, with no apparent cytotoxicity observed in vitro in the MTS assay. These findings underscore the potential of pyrazoline‐derived RAGE antagonists as therapeutic agents for addressing age‐related disorders.

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Synthesis of new hydrazone derivatives and evaluation of their monoamine oxidase inhibitory activity

Cited by 35 publications

References 37 publications

Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

Design, synthesis, biological activity, molecular docking, and molecular dynamics of novel benzimidazole derivatives as potential AChE/MAO‐B dual inhibitors

Ultrasound‐Assisted Synthesis of Pyrazoline Derivatives as Potential Antagonists of RAGE‐Mediated Pathologies: Insights from SAR Studies and Biological Evaluations

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