In vitro and in silico evaluation of new thiazole compounds as monoamine oxidase inhibitors

Sağlık, Begüm Nurpelin; Çavuşoğlu, Betül Kaya; Osmaniye, Derya; Levent, Serkan; Çevik, Ulviye Acar; Ilgın, Sinem; Özkay, Yusuf; Kaplancıklı, Zafer Asım; Öztürk, Yusuf

doi:10.1016/j.bioorg.2018.12.019

Cited by 56 publications

(32 citation statements)

References 36 publications

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“…The synthesis of the compounds was completed using well established methods [ 14 , 27 ]. The synthetic pathways of target compounds were summarized in Scheme 1 and Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Enzymatic testing was conducted using the current fluorometric approach declared by our research community [ 14 , 15 , 16 , 17 , 18 ]. Sigma-Aldrich (Steinheim, Germany) provided the chemicals and reagents used in the test (AmplifluTM Red (10-Acetyl-3,7-dihydroxyphenoxazine), MAO-A, MAO-B, peroxidase from horseradish, tyramine hydrochloride, H 2 O 2 , moclobemide, clorgiline and selegiline) and they were maintained by the manufacturer under the specified conditions.…”

Section: Methodsmentioning

confidence: 99%

“…The same materials were used in the MAO inhibition assay. In keeping with the assay given in our previous research, the most active compound, 3e , defined as a consequence of the MAO inhibition assay, was experienced in three independent concentrations of IC 50 /2, IC 50 and 2(IC 50 ) [ 14 , 15 , 16 , 17 , 18 ]. All processes were evaluated in quadruplicate.…”

Section: Methodsmentioning

confidence: 99%

“…In many studies, in which our team has been involved in recent years, many thiazolylhydrazine derivatives have been shown to exhibit MAO inhibitory activity in the micromolar concentration range [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. This study was carried out in order to further the activities of the compounds synthesized by our team and showing MAO-A activity in our previous studies.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

et al. 2020

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Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as 1H-NMR, 13C-NMR and HRMS. Moreover, the prediction of ADME (Absorption, Distribution, Metabolism, Elimination) parameters for all of the compounds were performed using in silico method. According to the enzyme inhibition results, the synthesized compounds showed the selectivity against MAO-A enzyme inhibition. Compounds 3c, 3d and 3e displayed significant MAO-A inhibition potencies. Among them, compound 3e was found to be the most effective derivative with an IC50 value of 0.057 ± 0.002 µM. Moreover, it was seen that this compound has a more potent inhibition profile than the reference inhibitors moclobemide (IC50 = 6.061 ± 0.262 µM) and clorgiline (IC50 = 0.062 ± 0.002 µM). In addition, the enzyme kinetics were performed for compound 3e and it was determined that this compound had a competitive and reversible inhibition type. Molecular modeling studies aided in the understanding of the interaction modes between this compound and MAO-A. It was found that compound 3e had significant and important binding property.

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“…The synthesis of the compounds was completed using well established methods [ 14 , 27 ]. The synthetic pathways of target compounds were summarized in Scheme 1 and Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

et al. 2020

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“…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

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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.

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Determination of the inhibition profiles of pyrazolyl–thiazole derivatives against aldose reductase and α‐glycosidase and molecular docking studies

Demir

Taslimi

Koçyiğit

et al. 2020

Archiv der Pharmazie

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Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH-dependent reaction. α-Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl-thiazoles ((3aR,4S,7R,7aS)-2-(4-{1-[4-(4-bromophenyl) thiazol-2-yl]-5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl}phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives; 3a-i) on AR and α-glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α-glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a K i value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a K i value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α-glycosidase, with K i values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the K i value of acarbose was 12.60 ± 0.78 µM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α-glycosidase. In addition, the ADME analysis of the molecules was performed.

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In vitro and in silico evaluation of new thiazole compounds as monoamine oxidase inhibitors

Cited by 56 publications

References 36 publications

Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

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

Determination of the inhibition profiles of pyrazolyl–thiazole derivatives against aldose reductase and α‐glycosidase and molecular docking studies

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