scholarly journals Study of Monoamine Oxidase-B and Indole Derivatives Using Two Molecular Docking Programs: Molegro and MOE

2020 ◽  
Vol 8 (09) ◽  
pp. 25-31
Author(s):  
W. Soufi ◽  
M. Merad ◽  
F. BOUKLI Hacene ◽  
S. Ghalem
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Molecular Modeling ◽  
Monoamine Oxidase ◽  
Indole Derivatives ◽  
Modeling Tools ◽  
Molegro Virtual Docker ◽  
Mao B ◽  
Modeling Methods

Inhibition of the enzyme Monoamine oxidase (MAO) is an important approach in the treatment of Parkinson’s disease. A series of indole derivatives were synthesised and evaluated as inhibitors of MAO-B may give insight to develop new ways of antiparkinson drug, In general, the derivatives were found to be selective MAO-B inhibitors with IC50 values . MAO-B inhibitors,  are considered useful in the therapy of Parkinson’s disease since oxidation by MAO-B represents a major catabolic pathway of dopamine in the central nervous system .                      Our goal of research is to study the inhibition of MAO-B by molecular modeling methods. Different molecular modeling tools are used to perform this work (molecular mechanics, molecular dynamics and molecular docking by two programms MDV ( molegro virtual docker) and MOE (modelling Opering Environment. The results obtained from this work, into which the inhibition of MAO-B by molecular modeling methods was elucidated, allow us to conclude that indole derivatives are promising reversible MAO-B inhibitors with a possible role in the treatment of neurodegenerative diseases such as Parkinson’s disease (PD). 

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 Comparative effectiveness of dopamine agonists and monoamine oxidase type-B inhibitors for Parkinson’s disease: a multiple treatment comparison meta-analysis

2020 ◽  
Vol 76 (12) ◽  
pp. 1731-1743
Author(s):  
Caroline D. Binde ◽  
Ingunn F. Tvete ◽  
Jørund I. Gåsemyr ◽  
Bent Natvig ◽  
Marianne Klemp
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Comparative Effectiveness ◽  
Dopamine Agonists ◽  
Relative Effectiveness ◽  
Type B ◽  
Mao B ◽  
Treatment Comparison ◽  
Monoamine Oxidase Type B

Abstract Purpose To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson’s disease. Methods We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson’s disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson’s Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug. Results Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment. Conclusions Dopamine agonists were found to be effective as treatment for Parkinson’s disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson’s disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.

Evaluation of Selected Natural Compounds as Dual Inhibitors of Catechol-O-Methyltransferase and Monoamine Oxidase

2019 ◽  
Vol 19 (2) ◽  
pp. 133-145 ◽  
Author(s):  
Idalet Engelbrecht ◽  
Jacobus P. Petzer ◽  
Anél Petzer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Symptomatic Treatment ◽  
Natural Compounds ◽  
Comt Inhibition ◽  
Comt Inhibitors ◽  
Mao B ◽  
Dual Inhibitors

Background: The most effective symptomatic treatment of Parkinson’s disease remains the metabolic precursor of dopamine, L-dopa. To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Objective: This study attempted to discover compounds that exhibit dual inhibition of COMT and MAO-B among a library of 40 structurally diverse natural compounds. Such dual acting inhibitors may be effective as adjuncts to L-dopa and offer enhanced value in the management of Parkinson’s disease. Methods: Selected natural compounds were evaluated as in vitro inhibitors of rat liver COMT and recombinant human MAO. Reversibility of MAO inhibition was investigated by dialysis. Results: Among the natural compounds morin (IC50 = 1.32 µM), chlorogenic acid (IC50 = 6.17 µM), (+)-catechin (IC50 = 0.86 µM), alizarin (IC50 = 0.88 µM), fisetin (IC50 = 5.78 µM) and rutin (IC50 = 25.3 µM) exhibited COMT inhibition. Among these active COMT inhibitors only morin (IC50 = 16.2 µM), alizarin (IC50 = 8.16 µM) and fisetin (IC50 = 7.33 µM) were noteworthy MAO inhibitors, with specificity for MAO-A. Conclusion: None of the natural products investigated here are dual COMT/MAO-B inhibitors. However, good potency COMT inhibitors have been identified, which may serve as leads for future development of COMT inhibitors.

Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson's disease: The degree and reversibility of human brain MAO B inhibition by Ro 19 6327

Neurology ◽  
1993 ◽  
Vol 43 (10) ◽  
pp. 1984-1984 ◽  
Author(s):  
J. S. Fowler ◽  
N. D. Volkow ◽  
J. Logan ◽  
D. J. Schlyer ◽  
R. R. MacGregor ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Human Brain ◽  
Inhibitor Therapy ◽  
Monoamine Oxidase B ◽  
Mao B

The Role of Monoamine Oxidase B Inhibitors in the Treatment of Parkinson’s Disease – An Update

2021 ◽  
Vol 21 ◽  
Author(s):  
Zhi Xin Chew ◽  
Chooi Ling Lim ◽  
Khuen Yen Ng ◽  
Soi Moi Chye ◽  
Anna Pick Kiong Ling ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Neuropsychiatric Symptoms ◽  
European Medicines Agency ◽  
Dopamine Level ◽  
Mao B ◽  
Sensory Disturbances ◽  
Non Motor Symptoms

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by reduced dopamine level in the substantial nigra. This may lead to typical motor features such as bradykinesia, resting tremors and rigid muscles; as well as non-motor symptoms such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, and sensory disturbances. Inhibitors of MAO-B are used to alleviate symptoms by reducing monoamine oxidase-catalysed degradation of dopamine; hence, preserving functional levels of dopamine. The very first MAO-B used therapeutically was selegiline, followed by rasagiline, its indane derivative which has superior efficacy and selectivity. Both inhibitors can be used as monotherapy or in combination with other anti-Parkinson drugs. Safinamide, a reversible MAO-B inhibitor that utilises both dopaminergic and non-dopaminergic mechanisms, was recently approved by the European Medicines Agency (EMA) (2015) and U.S. FDA (2017) as an add-on therapy for patients with mid- or late-stage Parkinson’s disease. Furthermore, MAO-B inhibitors were found to be associated with potential neuroprotective and disease modifying effects. However, evidence of their efficacy and role in PD models are scarce and warrants further investigation.

Identification of Novel Phyto-chemicals from Ocimum basilicum for the Treatment of Parkinson’s Disease using In Silico Approach

2020 ◽  
Vol 16 (4) ◽  
pp. 420-434
Author(s):  
Nageen Mubashir ◽  
Rida Fatima ◽  
Sadaf Naeem
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Active Site ◽  
In Silico ◽  
Chemical Constituents ◽  
Docking Studies ◽  
Ocimum Basilicum ◽  
Mao B

Background: Parkinson’s disease is characterized by decreased level of dopaminergic neurotransmitters and this decrease is due to the degradation of dopamine by protein Monoamine Oxidase B (MAO-B). In order to treat Parkinson’s disease, MAO-B should be inhibited. Objective: To find out the novel phytochemicals from plant Ocimum basilicum that can inhibit MAO-B by using the in silico methods. Methods: The data of chemical constituents from plant Ocimum basilicum was collected and inhibitory activity of these phytochemicals was then predicted by using the Structure-Based (SB) and Ligand-Based Virtual Screening (LBVS) methods. Molecular docking, one of the common Structure-Based Virtual Screening method, has been used during this search. Traditionally, molecular docking is used to predict the orientation and binding affinity of the ligand within the active site of the protein. Molegro Virtual Docker (MVD) software has been used for this purpose. On the other hand, Random Forest Model, one of the LBVS method, has also been used to predict the activity of these chemical constituents of Ocimum basilicum against the MAO-B. Results: During the docking studies, all the 108 compounds found in Ocimum basilicum were docked within the active site of MAO-B (PDB code: 4A79) out of which, 57 compounds successfully formed the hydrogen bond with tyr 435, a crucial amino acid for the biological activity of the enzyme. Rutin (-182.976 Kcal/mol), Luteolin (-163.171 Kcal/mol), Eriodictyol-7-O-glucoside (- 160.13 Kcal/mol), Rosmarinic acid (-133.484 Kcal/mol) and Isoquercitrin (-131.493 Kcal/mol) are among the top hits with the highest MolDock score along with hydrogen interaction with tyr 435. Using the RF model, ten compounds out of 108 chemical constituent of Ocimum basilicum were predicted to be active, Apigenin (1.0), Eriodictyol (1.0), Orientin (0.876), Kaempferol (0.8536), Luteolin (0.813953) and Rosmarinic-Acid (0.7738095) are predicted to be most active with the highest RF score. Conclusion: The comparison of the two screening methods show that the ten compounds that were predicted to be active by the RF model, are also found in top hits of docking studies with the highest score. The top hits obtained during this study are predicted to be the inhibitor of MAO-B, thus, could be used further for the development of drugs for the treatment of Parkinson’s disease (PD).

scholarly journals Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson’s Disease: Past, Present, and Future

2021 ◽  
pp. 1-17
Author(s):  
Yu-Yan Tan ◽  
Peter Jenner ◽  
Sheng-Di Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Early Stage ◽  
Symptomatic Treatment ◽  
Monoamine Oxidase B ◽  
Motor Symptoms ◽  
Mao B ◽  
Advanced Stages ◽  
Non Motor Symptoms

Monoamine oxidase-B (MAO-B) inhibitors are commonly used for the symptomatic treatment of Parkinson’s disease (PD). MAO-B inhibitor monotherapy has been shown to be effective and safe for the treatment of early-stage PD, while MAO-B inhibitors as adjuvant drugs have been widely applied for the treatment of the advanced stages of the illness. MAO-B inhibitors can effectively improve patients’ motor and non-motor symptoms, reduce “OFF” time, and may potentially prevent/delay disease progression. In this review, we discuss the effects of MAO-B inhibitors on motor and non-motor symptoms in PD patients, their mechanism of action, and the future development of MAO-B inhibitor therapy.

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