Design, Synthesis and hMAO Inhibitory Screening of Novel 2-Pyrazoline Analogues

Evranos-Aksöz, Begüm; Uçar, Gülberk; Yelekçi, Kemal

doi:10.2174/1386207320666170504114208

Cited by 7 publications

(3 citation statements)

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“…Various generations of MAO inhibitors have been developed with the aim of decreasing their adverse side effects such as hypertensive crisis, liver toxicity, and sleep disturbance and headache, as observed with some MAO‐A inhibitors. Starting more than 50 years ago with hydrazine derivatives (e.g., iproniazide) and then propargylamine derivatives (clorgyline, deprenyl, rasagiline), the latest generation of MAO inhibitors includes a wide variety of chemotypes obtained from synthetic compounds or natural products, such as chalcones, pyrazoles, chromones, coumarins, isatin derivatives, thiazolidindiones, and polyamine analogues . In particular, the most recent efforts have involved the development of reversible and MAO‐B‐selective compounds, such as safinamide ( K i ca.…”

Section: Introductionmentioning

confidence: 99%

2‐Phenyloxazole‐4‐carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

et al. 2019

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A series of 2‐phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO‐B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub‐micromolar range and a good selectivity index (Ki MAO‐A/Ki MAO‐B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)‐differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2‐(2‐hydroxyphenyl)‐N‐phenyloxazole‐4‐carboxamide (compound 4 a) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF‐differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.

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Section: Introductionmentioning

confidence: 99%

2‐Phenyloxazole‐4‐carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

et al. 2019

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“…These ring systems inhibit cyclooxygenase enzymes, particularly the COX-2 enzyme [10][11][12][13][14][15][16]. It is thought that these compounds, whose antidepressant and antimicrobial activities we have previously published [17][18][19], may inhibit the COX enzymes because of their similarity to celecoxib (Figure 1), which is a selective COX-2 inhibitor in terms of chemical structure and also carrying a 4,5-dihydro-1Hpyrazole ring in their structure. In this study, molecular docking interactions of some 4,5-dihydro-1Hpyrazole derivatives with COX-1 and COX-2 enzymes were investigated.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking Studies on Some 4,5-Dihydro-1h-Pyrazole Derivatives as Cyclooxygenase Inhibitors

Aksöz¹

2021

Ankara Universitesi Eczacilik Fakultesi Dergisi

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Objective: To examine the interactions of some 4,5-dihydro-1H-pyrazole derivatives, which are thought to have antiinflammatory effects, with cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, docking studies were carried out on these enzymes.Material and Method: COX-1 enzyme (3KK6) and COX-2 enzyme (3LN1) were selected from the protein data bank for docking studies. The ligand and protein constructs were prepared using Autodock 1.5.6. AutoDock Vina was used to determining the binding affinity, and Discovery Studio 3.5 was utilised to analyse and display the docking results.Result and Discussion: As a result of the docking process on COX-1 and COX-2 enzymes, 4,5-Dihydro-1H-pyrazole derivatives were observed to interact with both enzymes. The 4,5-dihydro-1H-pyrazole ring was found to be important in its interactions with the COX-2 enzyme. The inclusion of a bulky group in the construct did not cause any problems in interaction with the COX-1 enzyme but eliminated some interactions with the COX-2 enzyme. To better elucidate the inhibition properties of enzymes, this study should be supported by in vitro and in vivo COX inhibition tests.

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“…MAO inhibitors are a useful tool for the treatment of many neurological and psychiatric diseases. In particular, reversible and selective MAO A inhibitors are employed in the treatment of certain mental disorders as antidepressant and antianxiety drugs, while inhibition of MAO B enzyme is related with treatment of Parkinson and Alzheimer disease …”

Section: Introductionmentioning

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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Design, Synthesis and hMAO Inhibitory Screening of Novel 2-Pyrazoline Analogues

Cited by 7 publications

References 0 publications

2‐Phenyloxazole‐4‐carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

2‐Phenyloxazole‐4‐carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

Molecular Docking Studies on Some 4,5-Dihydro-1h-Pyrazole Derivatives as Cyclooxygenase Inhibitors

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

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