Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity

Can, Nafiz Öncü; Osmaniye, Derya; Levent, Serkan; Sağlık, Begüm Nurpelin; İnci, Beril; Ilgın, Sinem; Özkay, Yusuf; Kaplancıklı, Zafer Asım

doi:10.3390/molecules22081381

Cited by 52 publications

(46 citation statements)

References 35 publications

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“…Hydrazide-hydrazones are known as antitumor [30][31][32] and antimicrobial agents [33][34][35], as well as enzyme inhibitors [31,[36][37][38][39][40][41]. Hydrazones are less recognized as inhibitors of metallo-enzymes and only the rare examples can be found in the literature so far [38,[40][41][42][43].…”

Section: Syntheses and Characterizationsmentioning

confidence: 99%

Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor

et al. 2020

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A series of hydrazide-hydrazones 1–3, the imine derivatives of hydrazides and aldehydes bearing benzene rings, were screened as inhibitors of laccase from Trametes versicolor. Laccase is a copper-containing enzyme which inhibition might prevent or reduce the activity of the plant pathogens that produce it in various biochemical processes. The kinetic and molecular modeling studies were performed and for selected compounds, the docking results were discussed. Seven 4-hydroxybenzhydrazide (4-HBAH) derivatives exhibited micromolar activity Ki = 24–674 µM with the predicted and desirable competitive type of inhibition. The structure–activity relationship (SAR) analysis revealed that a slim salicylic aldehyde framework had a pivotal role in stabilization of the molecules near the substrate docking site. Furthermore, the presence of phenyl and bulky tert-butyl substituents in position 3 in salicylic aldehyde fragment favored strong interaction with the substrate-binding pocket in laccase. Both 3- and 4-HBAH derivatives containing larger 3-tert-butyl-5-methyl- or 3,5-di-tert-butyl-2-hydroxy-benzylidene unit, did not bind to the active site of laccase and, interestingly, acted as non-competitive (Ki = 32.0 µM) or uncompetitive (Ki = 17.9 µM) inhibitors, respectively. From the easily available laccase inhibitors only sodium azide, harmful to environment and non-specific, was over 6 times more active than the above compounds.

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Section: Syntheses and Characterizationsmentioning

confidence: 99%

Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor

et al. 2020

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“…The cells were incubated as reported in the supplier's guide. The MTT assay was applied according to our previous studies [32][33][34]. The IC 50 values of compounds i and s were calculated from the plots of cell proliferation against concentrations by applying regression analyses on GraphPad Prism Version 5.…”

Section: Cytotoxicity Testmentioning

confidence: 99%

Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors

Can

Çevik

Sağlık

et al. 2017

Journal of Chemistry

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Due to anticandidal importance of azole compounds, a new series of benzimidazole-triazole derivatives ( a-s) were designed and synthesized as ergosterol inhibitors. The chemical structures of the target compounds were characterized by spectroscopic methods. The final compounds were screened for antifungal activity against Candida glabrata (ATCC 90030), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019), and Candida albicans (ATCC 24433). Compounds i and s exhibited significant inhibitory activity against Candida strains with MIC 50 values ranging from 0.78 to 1.56 g/mL. Cytotoxicity results revealed that IC 50 values of compounds i and s against NIH/3T3 are significantly higher than their MIC 50 values. Effect of the compounds i and s against ergosterol biosynthesis was determined by LC-MS-MS analysis. Both compounds caused a significant decrease in the ergosterol level. The molecular docking studies were performed to investigate the interaction modes between the compounds and active site of lanosterol 14--demethylase (CYP51), which is as a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for final compounds.

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“…Assay. MAO enzyme inhibition assay, based on fluorometric measurements, was used to determine the inhibition profiles of all synthesized compounds as previously defined by us [15,16]. e reagents used in the enzymatic assay including Ampliflu ™ Red (10-acetyl-3,7-dihydroxyphenoxazine), peroxidase from horseradish, hMAO-A, hMAO-B, H 2 O 2 , tyramine hydrochloride, selegiline, and moclobemide were purchased from Sigma-Aldrich (Steinheim, Germany).…”

Section: Mao-a and Mao-b Inhibitionmentioning

confidence: 99%

“…In order to investigate the inhibition type of compound 4b on hMAO-B, enzyme kinetic study was applied according to the previous studies reported by us [15,16].…”

Section: Enzyme Kinetic Studiesmentioning

confidence: 99%

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Synthesis and Evaluation of N-[1-(((3,4-Diphenylthiazol-2(3H)-ylidene)amino)methyl)cyclopentyl]acetamide Derivatives for the Treatment of Diseases Belonging to MAOs

Turan-Zitouni

Tabbi

Hussein

et al. 2018

Journal of Chemistry

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A series of N-[1-(((3,4-diphenylthiazol-2(3H)-ylidene)amino)methyl)cyclopentyl]acetamide derivatives (4a-4i) were synthesized in good yield and assayed for their inhibitory potency against monoamine oxidase (MAO) isoforms. Structures of newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, and mass spectroscopic methods. The inhibitory activity of compounds (4a-4i) against hMAO-A and hMAO-B enzymes was elucidated by using in vitro fluorometric method using Amplex Red® reagent. In the hMAO-A inhibition assay, compounds 4a, 4b, 4c, and 4i exhibited similar activity with standard drug moclobemide (IC50 = 6.061 ± 0.262 µM) with IC50 values of 7.06 ± 0.18 µM, 6.56 ± 0.20 µM, 6.78 ± 0.15 µM, and 7.09 ± 0.17 µM, respectively. According to hMAO-B inhibition results, compounds 4a, 4b, and 4c displayed significant activity with IC50 values of 0.42 ± 0.012 µM, 0.36 ± 0.014 µM, and 0.69 ± 0.020 µM, respectively. In the wake of all these results, it was understood that compound 4b was found to be the most potent derivative in the series against both isoforms and selective as MAO-B inhibitor. The cytotoxicity test was performed for compounds 4a, 4b, and 4c, and it was found that these compounds were noncytotoxic at the concentration of their IC50 values. Also, enzyme kinetic and docking studies of compound 4b were performed against MAO-B. It was observed that 4b showed a reversible and noncompetitive inhibition type. The important binding modes of this compound with active site of hMAO-B were shown owing to in silico studies.

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Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity

Cited by 52 publications

References 35 publications

Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor

Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor

Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors

Synthesis and Evaluation of N-[1-(((3,4-Diphenylthiazol-2(3H)-ylidene)amino)methyl)cyclopentyl]acetamide Derivatives for the Treatment of Diseases Belonging to MAOs

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