scholarly journals 4-Phenethyl-1-Propargylpiperidine-Derived Dual Inhibitors of Butyrylcholinesterase and Monoamine Oxidase B

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4118
Author(s):  
Tjaša Mazej ◽  
Damijan Knez ◽  
Anže Meden ◽  
Stanislav Gobec ◽  
Matej Sova
Keyword(s):  
Monoamine Oxidase ◽  
Docking Studies ◽  
Monoamine Oxidase B ◽  
Mao B ◽  
Initial Expectation ◽  
Excellent Starting Point ◽  
Starting Point ◽  
Dependent Inhibition ◽  
Dual Inhibitors ◽  
Time Dependent Inhibition

The multi-target-directed ligands (MTDLs) strategy is encouraged for the development of novel modulators targeting multiple pathways in the neurodegenerative cascade typical for Alzheimer’s disease (AD). Based on the structure of an in-house irreversible monoamine oxidase B (MAO-B) inhibitor, we aimed to introduce a carbamate moiety on the aromatic ring to impart cholinesterase (ChE) inhibition, and to furnish multifunctional ligands targeting two enzymes that are intricately involved in AD pathobiology. In this study, we synthesized three dual hMAO-B/hBChE inhibitors 13–15, with compound 15 exhibiting balanced, low micromolar inhibition of hMAO-B (IC50 of 4.3 µM) and hBChE (IC50 of 8.5 µM). The docking studies and time-dependent inhibition of hBChE confirmed the initial expectation that the introduced carbamate moiety is responsible for covalent inhibition. Therefore, dual-acting compound 15 represents an excellent starting point for further optimization of balanced MTDLs.

New indane derivatives containing 2-hydrazinothiazole as potential acetylcholinesterase and monoamine oxidase-B inhibitors

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
İsmail Okan Ateş ◽  
Asaf Evrim Evren ◽  
Begüm Nurpelin Sağlik ◽  
Leyla Yurttaş
Keyword(s):  
Monoamine Oxidase ◽  
Cholinesterase Inhibitors ◽  
Life Quality ◽  
Monoamine Oxidase B ◽  
Thiazole Derivatives ◽  
Mao B ◽  
H Nmr ◽  
Dual Inhibitors ◽  
C Nmr

Abstract Although radical treatment of Alzheimer’s and Parkinson’s disease is not possible yet, it is aimed to slow the course of the disease and increase the life quality of individuals with the drugs used in the clinic at the present time. Successful results have been achieved in the use of cholinesterase inhibitors and monoamine oxidase inhibitors together in these neurodegenerative diseases. In this study, indane ring which are in the structure of anticholinesterase effective molecules and 2-hydrazinothiazole structure whose inhibitory activities reported on monoamine oxidase-B (MAO-B) were combined; 4-(substituted phenyl)-2-[2-(3-phenyl-2,3-dihydro-1H-inden-1-ylidene) hydrazinyl]thiazole derivatives (3a–3i) were synthesized as dual inhibitors. The structures of the compounds were verified by IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. When enzyme inhibition activities were evaluated, it was determined that the compounds 3a (42.33%) and 3d (42.39%) on acetylcholinesterase (AChE) enzyme; compounds 3g (75.42%) and 3h (60.33%) showed inhibition on MAO-B enzyme at most, at 10−3 M concentration.

scholarly journals VIRTUAL SCREENING OF GINKGO BILOBA FOR THERAPEUTIC POTENTIALS AGAINST PARKINSON’S DISEASE

2016 ◽  
Vol 3 (1) ◽  
pp. 6-11
Author(s):  
Kavitha V ◽  
Jone Kirubavathy S ◽  
Sivaramkumar M.S ◽  
Velmurugan R
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Ginkgo Biloba ◽  
Neurodegenerative Disorder ◽  
Docking Studies ◽  
Monoamine Oxidase B ◽  
Mao B ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder that affects 2% of the population older than 60 years. Monoamine Oxidase B (MAO-B) inhibitors improve the symptoms of Parkinson's disease and can delay the progress. Inhibition of MAO-B, further prevent breakdown of dopamine in the brain and reducethe motor symptoms associated with PD. Ginkgo biloba has a number of therapeutic properties and contains phytonutrients that helps in improvement of neurological disorders. In present study, phytonutrients of Ginkgo biloba namely Myricetin, Quercetin, Isorhamnetin, Kaempferol, Ginkgolides A-C, and Ginkgolide J were selected for Molecular docking against Monoamine Oxidase-B enzyme. The Molecular Docking studies were performed using Autodock 4.2 and interaction between MAO-B and compounds were analyzed. The efficiency of the compound was screened based on the binding energy existing between the protein and inhibitor. The docking studies show that the phytochemicals of Ginkgo biloba against MAO-B were quite effective. The potential compound can be subjected to further clinical trials and can be an alternative in the future treatment of Parkinson’s disease.

▼ Safinamide for Parkinson’s disease

2018 ◽  
Vol 56 (5) ◽  
pp. 54-57
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Motor Fluctuations ◽  
Daily Activities ◽  
Monoamine Oxidase B ◽  
Motor Symptoms ◽  
Idiopathic Parkinson’S Disease ◽  
Mao B ◽  
Idiopathic Parkinson's Disease

▼ Safinamide (Xadago - Zambon S.p.A) is a monoamine-oxidase B (MAO-B) inhibitor licensed as add-on therapy for people with idiopathic Parkinson’s disease who are experiencing motor fluctuations with levodopa.1 Currently there is no cure for Parkinson’s disease and drugs are used to reduce motor symptoms and improve daily activities.2,3 Here, we review the evidence for this MAO-B inhibitor.

scholarly journals Coumarin analogue 3-methyl-7H-furo[3,2-g] chromen-7-one as a possible antiparkinsonian agent

Biomédica ◽  
2019 ◽  
Vol 39 (3) ◽  
pp. 491-501
Author(s):  
María del Pilar Olaya ◽  
Nadezdha Esperanza Vergel ◽  
José Luis López ◽  
María Dolores Viña ◽  
Mario Francisco Guerrero
Keyword(s):  
Antioxidant Activity ◽  
Monoamine Oxidase ◽  
Mouse Models ◽  
Inhibitory Activity ◽  
Ex Vivo ◽  
Monoamine Oxidase B ◽  
Mao B ◽  
Continue Research ◽  
Substituted Coumarins

Introduction: Parkinson’s disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B.Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity.Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively.Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity.Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

scholarly journals CYP-Dependent Metabolism of PF9601N, A New Monoamine Oxidase-B Inhibitor, by C57BL / 6 Mouse and Human Liver Microsomes

2007 ◽  
Vol 10 (4) ◽  
pp. 473 ◽  
Author(s):  
Stefania Dragoni ◽  
Giada Materozzi ◽  
Federica Pessina ◽  
Maria Frosini ◽  
José Luis Marco ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Human Liver ◽  
Formation Rate ◽  
Antioxidant Properties ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Human Liver Microsomes ◽  
Monoamine Oxidase B ◽  
Mao B

Purpose. The selective monoamine oxidase-B (MAO-B) inhibitor, l-deprenyl, is still used for treating Parkinson's patients, however, a disadvantage of its use lies in the formation of l-amphetamine and l-methamphetamine. Subsequently, this has promoted the design of a novel, more potent, MAO-B inhibitor PF9601N, which also has neuroprotective and antioxidant properties. The aim of this work was to investigate the effect of treatment with PF9601N on its own phase I hepatic metabolism. Kinetic parameters of PF9601N CYP-dependent N-dealkylation reaction was also studied and compared with those of l-deprenyl. Methods. C57BL/6 mice were treated with PF9601N for 4 days. After CYP content and related monooxygenase activities were assayed in liver microsomes of control and treated animals. Results. CYP activities, cytochrome b5 content, NADPH-cytochrome P450 reductase and various monooxygenase activities were unaffected by in vivo PF9601N treatment. With microsomes from both control and treated mice, the PF9601N-dealkylation product, FA72, was the only detected metabolite with its formation rate following an hyperbolic, Michaelis-Menten curve. Among various inhibitors, only ketoconazole inhibited the FA72 formation rate, indicating a major involvement for CYP3A. Apparent Km and Vmax values generated by human liver microsomes were similar to those found with mouse microsomes. Ketoconazole inhibition indicates that CYP3A is one of the major enzymes involved in PF9601N metabolism also by human liver microsomes. In mouse liver microsomes, the intrinsic clearance of PF9601N was significantly lower than that of l-deprenyl suggestive of an improved bioavailability for the former. Conclusion. The observed favourable metabolic profile may suggest suitability of PF9601N for clinical use.

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