New Human Monoamine Oxidase A Inhibitors with Potential Anti- Depressant Activity: Design, Synthesis, Biological Screening and Evaluation of Pharmacological Activity

Evranos-Aksöz, Begüm; Uçar, Gülberk; Tas, Sadik Taskin; Aksöz, Erkan; Yelekçi, Kemal; Erikçi, Açelya; Sara, Yıldırım; İskit, Alper B.

doi:10.2174/1386207320666170504113158

Cited by 8 publications

(5 citation statements)

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“…To avoid any scent‐induced cues, surfaces and equipment were cleaned between each experiment with 70% ethanol solution. Animal tracking and recording was performed using in‐house‐developed tracking software (Yucel et al, ; Evranos‐Aksoz et al, ).…”

Section: Methodsmentioning

confidence: 99%

High‐fructose corn syrup consumption in adolescent rats causes bipolar‐like behavioural phenotype with hyperexcitability in hippocampal CA3‐CA1 synapses

Alten

Yeşiltepe

Bayraktar

et al. 2018

British J Pharmacology

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Section: Methodsmentioning

confidence: 99%

High‐fructose corn syrup consumption in adolescent rats causes bipolar‐like behavioural phenotype with hyperexcitability in hippocampal CA3‐CA1 synapses

Alten

Yeşiltepe

Bayraktar

et al. 2018

British J Pharmacology

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“…At the same time, the length and bulkiness of the groups anchoring from the N1 position of pyrazolines can shift the selectivity from MAO-B to MAO-A. The presence of lipophilic groups, such as halogens, hydroxyl, and methoxy groups, on the phenyl ring of the third and fifth positions of the pyrazoline nucleus, can cause significant MAO-B inhibition [ 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach

Nair

Koyiparambath

et al. 2021

Molecules

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Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (EH7) showed the highest potency against MAO-B with an IC50 value of 0.063 µM. The potencies against MAO-B were increased in the order of –F (in EH7) > –Cl (EH6) > –Br (EH8) > –H (EH1). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for EH7 and EH8 (IC50 = 8.38 and 4.31 µM, respectively). EH7 showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by EH6 at > 55.8. EH7 was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that EH7 had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of EH7 to MAO-B. Thus, EH7 can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.

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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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New Human Monoamine Oxidase A Inhibitors with Potential Anti- Depressant Activity: Design, Synthesis, Biological Screening and Evaluation of Pharmacological Activity

Cited by 8 publications

References 0 publications

High‐fructose corn syrup consumption in adolescent rats causes bipolar‐like behavioural phenotype with hyperexcitability in hippocampal CA3‐CA1 synapses

High‐fructose corn syrup consumption in adolescent rats causes bipolar‐like behavioural phenotype with hyperexcitability in hippocampal CA3‐CA1 synapses

Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach

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

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