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https://www.readbyqxmd.com/read/28069864/hydralazine-is-involved-in-tele-methylhistamine-metabolism-by-inhibiting-monoamine-oxidase-b-in-pregnancy-associated-hypertensive-mice
#1
Shohei Kawasaki, Koichiro Kako, Yusuke Nagashima, Akihiko Kanou, Junji Ishida, Akiyoshi Fukamizu
Hypertensive disorders of pregnancy globally affect 6-8% of gestation and remain a major cause of both foetal and maternal morbidity and mortality. However, the antihypertensive medications for the patients of this disease are strictly limited due to the teratogenic potentials. Here, we found that tele-methylhistamine (tMH) increased in response to the administration of hydralazine (Hdz), a vasodilative agent, in the pregnancy-associated hypertensive (PAH) mice. Hdz abrogated the degradation of tMH catalyzed by monoamine oxidase B (MAO-B) in vitro These results suggested that Hdz inhibited the MAO-B activity and consequently tMH increased in the maternal circulation of PAH mice...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28069007/the-benzopyrone-biochanin-a-as-a-reversible-competitive-and-selective-monoamine-oxidase-b-inhibitor
#2
Najla O Zarmouh, Suresh K Eyunni, Karam F A Soliman
BACKGROUND: Monoamine oxidase-B (MAO-B) inhibitors are widely used in the treatment of Parkinson's disease. They increase vital monoamine neurotransmitters in the brain. However, there is a need for safer natural reversible MAO inhibitors with MAO-B selectivity. Our previous studies showed that Psoralea corylifolia seeds (PCS) extract contains compounds that inhibit monoamine oxidase-B. METHODS: In this study, six of PCS constituents sharing a benzopyrone structure were investigated...
January 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28068665/potent-inhibition-of-monoamine-oxidase-b-by-a-piloquinone-from-a-marine-derived-streptomyces-sp-cnq-027
#3
Hyun Woo Lee, Hansol Choi, Sang-Jip Nam, William Fenical, Hoon Kim
Two piloquinone derivatives isolated from Streptomyces sp. CNQ-027 were tested for the inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1-oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of human MAO-B, with an IC₅₀ value of 1.21 µM; in addition, it was found to be highly effective against MAO-A, with an IC₅₀ value of 6.47 µM. Compound 1 was selective, but not extremely so, for MAO-B compared to MAO-A, with a selectivity index value of 5...
January 9, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28067625/pituitary-adenylate-cyclase-activating-polypeptide-pacap-has-neuroprotective-function-in-dopamine-based-neurodegeneration-developed-in-two-parkinsonian-models
#4
G Maasz, Z Zrinyi, D Reglodi, D Petrovics, A Rivnyak, T Kiss, A Jungling, A Tamas, Z Pirger
It has been observed that pituitary-adenylate cyclase activating polypeptide (PACAP) rescued DAergic neurons from neurodegeneration and improved motor alterations induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently we investigated the molecular background of the neuroprotective effect of PACAP in DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. The behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7/DJ-1 protein contents were measured before and after PACAP-treatment in both models...
December 22, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28067172/fusing-docking-scoring-functions-improves-the-virtual-screening-performance-for-discovering-parkinson-s-disease-dual-target-ligands
#5
Yunierkis Perez-Castillo, Aliuska Morales Helguera, M Natália D S Cordeiro, Eduardo Tejera, Cesar Paz-Y-Miño, Aminael Sánchez-Rodríguez, Fernanda Borges, Maykel Cruz-Monteagudo
Virtual methodologies have become essential components of the drug discovery pipeline. Specifically, structure-based drug design methodologies exploit the 3D structure of molecular targets to discover new drug candidates through molecular docking. Recently, dual target ligands of the Adenosine A2A Receptor and Monoamine Oxidase B enzyme have been proposed as effective therapies for the treatment of Parkinson's disease. To the best of our knowledge, no theoretical study has been devoted to developing structure-based virtual screening methodologies for the discovery of dual A2AAR antagonists and MAO-B inhibitors...
January 9, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28052533/what-a-difference-a-methyl-group-makes-the-selectivity-of-monoamine-oxidase-b-towards-histamine-and-n-methylhistamine
#6
Aleksandra Maršavelski, Robert Vianello
Monoamine oxidase (MAO) enzymes catalyze the degradation of a very broad range of biogenic and dietary amines including many neurotransmitters in the brain, whose imbalance is extensively linked with the biochemical pathology of various neurological disorders. Although sharing around 70% sequence identity, both MAO A and B isoforms differ in substrate affinities and inhibitor sensitivities. Inhibitors that act on MAO A are used to treat depression, due to their ability to raise serotonin concentrations, while MAO B inhibitors decrease dopamine degradation and improve motor control in patients with Parkinson disease...
January 3, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28035939/could-mao-b-inhibitor-withdrawal-rather-than-nilotinib-benefit-explain-the-dopamine-metabolite-increase-in-parkinsonian-study-subjects
#7
Michael A Schwarzschild
No abstract text is available yet for this article.
December 23, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28034283/in-silico-studies-revealed-multiple-neurological-targets-for-the-antidepressant-molecule-ursolic-acid
#8
Rajeev K Singla, Luciana Scotti, Ashok K Dubey
BACKGROUND: Ursolic acid, a bioactive pentacyclic triterpenoid had been evaluated for its interaction with the neurological targets associated with antidepressant drugs. Current study was to mechanistically analyze the probable site of action for ursolic acid on the target proteins. METHODS: Ursolic acid has been docked with monoamine oxidase isoforms: MAO-A and MAO-B, LeuT (homologue of SERT, NET, DAT) and Human C-terminal CAP1 using GRIP docking methodology. RESULTS: Results revealed its non-selective antidepressant action with strong binding affinity towards LeuT and MAO-A proteins, which was found to be comparable with the reference ligands like chlorgyline, clomipramine, sertraline and deprenyl / selegiline...
December 29, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/28012396/antidepressant-like-effects-of-hydrolysable-tannins-of-terminalia-catappa-leaf-extract-via-modulation-of-hippocampal-plasticity-and-regulation-of-monoamine-neurotransmitters-subjected-to-chronic-mild-stress-cms
#9
Y Chandrasekhar, E M Ramya, K Navya, G Phani Kumar, K R Anilakumar
Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i...
December 21, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27977122/comparative-analysis-of-the-neurochemical-profile-and-mao-inhibition-properties-of-n-furan-2-ylmethyl-n-methylprop-2-yn-1-amine
#10
Philippe De Deurwaerdère, Claudia Binda, Rémi Corne, Cosima Leone, Aurora Valeri, Massimo Valoti, Rona R Ramsay, Yagamare Fall, José Marco-Contelles
The regulation of brain monoamine levels is paramount for cognitive functions, and the monoamine oxidase (MAO A and B) enzymes play a central role in these processes. The aim of this study was to evaluate whether the procognitive properties exerted by propargylamine N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA) are related to changes in monoamine content via MAO inhibition. In vivo microdialysis and ex vivo amine metabolite measurement demonstrated region-specific alterations in monoamine metabolism that differ from both of the classic MAO A and MAO B inhibitors, clorgyline and l-deprenyl, respectively...
December 30, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#11
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27923535/multitarget-drug-design-strategy-against-alzheimer-s-disease-homoisoflavonoid-mannich-base-derivatives-serve-as-acetylcholinesterase-and-monoamine-oxidase-b-dual-inhibitors-with-multifunctional-properties
#12
Yan Li, Xiaoming Qiang, Li Luo, Xia Yang, Ganyuan Xiao, Yunxiaozhu Zheng, Zhongcheng Cao, Zhipei Sang, Fu Su, Yong Deng
A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC50=2.49±0.08nM and 1.74±0.0581μM, respectively), good self- and Cu(2+)-induced Aβ1-42 aggregation inhibitory potency, antioxidant activity, biometal chelating ability and high BBB permeability...
January 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27914011/activation-of-alpha-7-nicotinic-acetylcholine-receptor-reduces-brain-edema-in-mice-with-ischemic-stroke-and-bone-fracture
#13
Dingquan Zou, Man Luo, Zhenying Han, Lei Zhan, Wan Zhu, Shuai Kang, Chen Bao, Zhao Li, Jeffrey Nelson, Rui Zhang, Hua Su
Stroke is an important risk factor for bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) improves, stroke recovery by attenuating inflammation. We hypothesized that activation of α-7 nAchR also improves the blood-brain barrier (BBB) integrity. Permanent distal middle cerebral artery occlusion (pMCAO) was performed on C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0...
December 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27911341/longer-duration-of-mao-b-inhibitor-exposure-is-associated-with-less-clinical-decline-in-parkinson-s-disease-an%C3%A2-analysis%C3%A2-of%C3%A2-net-pd-ls1
#14
Robert A Hauser, Ruosha Li, Adriana Pérez, Xuehan Ren, Dan Weintraub, Jordan Elm, John L Goudreau, John C Morgan, John Y Fang, Michael J Aminoff, Chadwick W Christine, Rohit Dhall, Chizoba C Umeh, James T Boyd, Natividad Stover, Maureen Leehey, Richard M Zweig, Anthony P Nicholas, Ivan Bodis-Wollner, Allison Willis, Karl Kieburtz, Barbara C Tilley
BACKGROUND: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients. OBJECTIVE: To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline. METHODS: The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27908752/n-propargylpiperidines-with-naphthalene-2-carboxamide-or-naphthalene-2-sulfonamide-moieties-potential-multifunctional-anti-alzheimer-s-agents
#15
Urban Košak, Damijan Knez, Nicolas Coquelle, Boris Brus, Anja Pišlar, Florian Nachon, Xavier Brazzolotto, Janko Kos, Jacques-Philippe Colletier, Stanislav Gobec
In the brains of patients with Alzheimer's disease, the enzymatic activities of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer's disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, we have designed, synthesized and biochemically evaluated a series of N-propargylpiperidines...
January 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27902880/monoamine-oxidase-inhibitory-activity-methyl-versus-chlorochalcone-derivatives
#16
Bijo Mathew, Gülberk Uçar, Githa Elizabeth Mathew, Sincy Mathew, Praseedha Kalatharakkal Purapurath, Fasil Moolayil, Smrithy Mohan, Sheeba Varghese Gupta
Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase-B (MAO-B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO-B (hMAO-B) inhibitors, two series of twenty chalcones containing electron-donating and electron-withdrawing substituents were synthesized. All compounds were found to be competitive, selective, and reversible inhibitors of hMAO-B except (2E)-1-(4-methylphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P7) and (2E)-1-(4-chlorophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P17), which were found to be selective inhibitors of hMAO-A...
December 16, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27896136/attention-deficit-hyperactivity-disorder-suffers-from-mitochondrial-dysfunction
#17
Poonam Verma, Alpana Singh, Dominic Ngima Nthenge-Ngumbau, Usha Rajamma, Swagata Sinha, Kanchan Mukhopadhyay, Kochupurackal P Mohanakumar
BACKGROUND: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population. METHODS: To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ(0)-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry...
December 2016: BBA Clinical
https://www.readbyqxmd.com/read/27863747/symmetrical-aryl-linked-bis-iminothiazolidinones-as-new-chemical-entities-for-the-inhibition-of-monoamine-oxidases-synthesis-in-vitro-biological-evaluation-and-molecular-modelling-analysis
#18
Naeem Abbas, Sumera Zaib, Syeda Mahwish Bakht, Aliya Ibrar, Imtiaz Khan, Sadaf Batool, Aamer Saeed, Jamshed Iqbal
The multifactorial nature of Parkinson's disease necessitates the development of new chemical entities with inherent ability to address key pathogenic processes. To this end, two series of new symmetrical 1,2- and 1,4-bis(2-aroyl/alkoylimino-5-(2-methoxy-2-oxoethylidene)-4-oxo-thiazolidin-3-yl)benzene derivatives (3a-g and 5a-e) were synthesized in good yields by the cyclization of 1,2- and 1,4-bis(N'-substituted thioureido)benzene intermediates with dimethyl acetylenedicarboxylate (DMAD) in methanol at ambient temperature...
November 9, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27855360/benzyloxynitrostyrene-analogues-a-novel-class-of-selective-and-highly-potent-inhibitors-of-monoamine-oxidase-b
#19
Mietha M Van der Walt, Gisella Terre'Blanche, Jacobus P Petzer, Anél Petzer
This study examines a series of novel 3-benzyloxy-β-nitrostyrene analogues as a novel class of inhibitors of the monoamine oxidase (MAO) enzymes. MAO inhibitors are considered useful for the treatment of depression and Parkinson's disease, and have recently attracted attention as potential therapeutic agents for a range of disorders including Alzheimer's disease, prostate cancer and certain cardiomyopathies. This study shows that the 3-benzyloxy-β-nitrostyrene analogues are potent inhibitors of the MAO-B isoform with IC50 values in the nanomolar range (39-565 nM)...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27845365/computational-drug-target-screening-through-protein-interaction-profiles
#20
Santiago Vilar, Elías Quezada, Eugenio Uriarte, Stefano Costanzi, Fernanda Borges, Dolores Viña, George Hripcsak
The development of computational methods to discover novel drug-target interactions on a large scale is of great interest. We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays...
November 15, 2016: Scientific Reports
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