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María Figueiredo-González, Patricia Reboredo-Rodríguez, Carmen González-Barreiro, Alegría Carrasco-Pancorbo, Jesús Simal-Gándara, Beatriz Cancho-Grande
The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from 'Brava' and 'Mansa', varieties recently identified from Galicia (northwestern Spain), were selected for in vitro screening to evaluate their capacity to inhibit key enzymes involved in Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (5-LOX)), major depressive disorder (MDD) and Parkinson's disease (PD) (monoamine oxidases: h MAO-A and h MAO-B respectively)...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sanna Rauhamäki, Pekka A Postila, Sanna Niinivehmas, Sami Kortet, Emmi Schildt, Mira Pasanen, Elangovan Manivannan, Mira Ahinko, Pasi Koskimies, Niina Nyberg, Pasi Huuskonen, Elina Multamäki, Markku Pasanen, Risto O Juvonen, Hannu Raunio, Juhani Huuskonen, Olli T Pentikäinen
Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson's disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry...
2018: Frontiers in Chemistry
Yerkebulan Orazbekov, Mohamed A Ibrahim, Serjan Mombekov, Radhakrishnan Srivedavyasasri, Ubaidilla Datkhayev, Bauyrzhan Makhatov, Narayan D Chaurasiya, Babu L Tekwani, Samir A Ross
Phytochemical analysis of the ethanolic extract of Maclura pomifera fruits yielded four new compounds ( I - IV ) along with eleven known compounds ( V - XV ). The crude extract exhibited significant activity towards cannabinoid receptors (CB1: 103.4% displacement; CB2: 68.8% displacement) and possibly allosteric interaction with δ and μ opioid receptors (-49.7 and -53.8% displacement, resp.). Compound I was found to be possibly allosteric for κ and μ opioid receptors (-88.4 and -27.2% displacement, resp...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Kira Mergemeier, Matthias Lehr
Recently, we have described an HPLC-UV assay for the evaluation of inhibitors of plasma amine oxidase (PAO) using 6-(5-phenyl-2H-tetrazol-2-yl)hexan-1-amine (4) as a new type of substrate. Now we studied, whether this compound or homologues of it can also function as substrate for related amine oxidases, namely diamine oxidase (DAO), monoamine oxidase A (MAO A) and monoamine oxidase B (MAO B). Among these substances, 4 was converted by DAO with the highest rate. The best substrate for MAO A and B was 4-(5-phenyl-2H-tetrazol-2-yl)butan-1-amine (2)...
March 15, 2018: Analytical Biochemistry
Ruben Smith, Michael Schöll, Elisabet Londos, Tomas Ohlsson, Oskar Hansson
Mixed pathologies of α-synuclein, β-amyloid and tau are relatively common in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). We therefore wanted to study the retention patterns of18 F-AV-1451 in PD, PD-dementia (PDD), and DLB. To do this 44 healthy controls, 11 non-demented patients with PD, 18 patients with PDD, and six patients with DLB underwent MRI and18 F-AV-1451 PET scanning and cognitive testing. We found that parietal18 F-AV-1451 retention was increased in patients with DLB compared to controls and PD patients, while18 F-AV-1451 uptake was reduced in the substantia nigra in PDD...
March 16, 2018: Scientific Reports
Carlo Cattaneo, Jaime Kulisevsky, Viviana Tubazio, Paola Castellani
INTRODUCTION: Chronic pain is an important yet overlooked non-motor symptom of Parkinson's disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms. OBJECTIVES: To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment...
March 14, 2018: Advances in Therapy
Bhupinder Kumar, Mohit Kumar, Ashish Ranjan Dwivedi, Vinod Kumar
Monoamine oxidase B (MAO-B) inhibitors are potential drug candidates for the treatment of various neurological disorders including Parkinson's disease. A total of 20 new propargyl-containing 2,4,6-trisubstituted pyrimidine derivatives were synthesized and screened for MAO inhibition using Amplex Red assays. All the synthesized compounds were found to be reversible and selective inhibitors of the MAO-B isoform at sub-micromolar concentrations. MVB3 was the most potent MAO-B inhibitor with an IC50 value of 0...
March 13, 2018: ChemMedChem
Michael Strupp, Ludwig Kraus, Franz Schautzer, Dan Rujescu
OBJECTIVES: Since oral betahistine has a very high first-pass effect (ca. 99%), metabolized by monoamine oxidases (MAO), the benefits of a high-dosage betahistine monotherapy were compared with those of a lower dosage of betahistine in combination with the MAO-B inhibitor (MAO-B) selegiline on the frequency of acute attacks of vertigo in patients with Menière's disease (MD). METHODS: Thirteen adults aged 40-75 years (mean 58.9 years; six females) had initially been treated with a high dosage of betahistine dihydrochloride for at least 1 year...
March 12, 2018: Journal of Neurology
Souravh Bais, Renu Kumari, Yash Prashar
BACKGROUND: sinapic acid (3, 5 di-methoxy 4-hydroxycinnamic acid) is a bioactive compound. Recent studies showed that it has a significant potential to attenuate various chemically induced Neurodegenerative toxicities. AIM: the present study investigates the potential of sinapic acid as neuromodulator and its effect on release of Monoamine Oxidase (MAO-A, MAO-B), TNF-α, Acetylcholine esterase Enzyme, in cognitive dysfunctions associated with experimental dementia...
March 9, 2018: CNS & Neurological Disorders Drug Targets
Sule Erol Gunal, Senel Teke Tuncel, Nesrin Gokhan Kelekci, Gulberk Ucar, Basak Yuce Dursun, Safiye Sag Erdem, Ilknur Dogan
Single enantiomers of the new 5-methyl-3-aryloxazolidine-2,4-diones have been obtained either by an asymmetric synthesis using the chiral pool strategy or by a semipreparative resolution of the racemic compound by HPLC on an optically active stationary phase. The single enantiomers were assayed for their in vitro monoamine oxidase (hMAO) inhibitory activity and selectivity. The most potent inhibitor among the studied compounds has been found as (5R)-3-phenyl-5-methyl-2,4-oxazolidinedione (compound 1-R) which appeared to be a good antidepressant drug candidate since it inhibited hMAO-A selectively, competitively and reversibly with Ki values in the micromolar range (0...
February 10, 2018: Bioorganic Chemistry
Rui Xu, Ganyuan Xiao, Yan Li, Hongyan Liu, Qing Song, Xiaoyu Zhang, Ziyi Yang, Yunxiaozhu Zheng, Zhenghuai Tan, Yong Deng
A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC50  = 0.29 ± 0.01 μM and 0.46 ± 0.02 μM, respectively), MAO-A (IC50  = 8...
February 21, 2018: Bioorganic & Medicinal Chemistry
Rituraj Niranjan, Kaushal Prasad Mishra, Ashwani Kumar Thakur
Cyclooxygenase-2 or COX-2 has been known to be crucial for Parkinson's disease (PD) pathogenesis; however, its exact role is still not known. We first time report that inhibition of COX-2 promotes 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced neuronal cell death via induction of autophagic mechanisms. We found that treatment with MPTP induced cell death of neuroblastoma cells SH-SY5Y in a dose dependent manner. Treatment of MPTP has also upregulated the expressions of autophagic proteins such as LC3, beclin, ATG-5, and p62...
March 1, 2018: Molecular Neurobiology
Farida Larit, Khaled M Elokely, Narayan D Chaurasiya, Samira Benyahia, Manal A Nael, Francisco León, Mohammad Sanad Abu-Darwish, Thomas Efferth, Yan-Hong Wang, Djamila Belouahem-Abed, Samir Benayache, Babu L Tekwani, Stephen J Cutler
BACKGROUND: Monoamine oxidases (MAOs) are outer mitochondrial membrane flavoenzymes. They catalyze the oxidative deamination of a variety of neurotransmitters. MAO-A and MAO-B may be considered as targets for inhibitors to treat neurodegenerative diseases and depression and for managing symptoms associated with Parkinson's and Alzheimer's diseases. PURPOSE: The objective was to evaluate the inhibitory effect of Hypericum afrum and Cytisus villosus against MAO-A and B and to isolate the compounds responsible for the MAO-inhibitory activity...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Anna Affini, Stefanie Hagenow, Aleksandra Zivkovic, Jose Marco-Contelles, Holger Stark
The design of multi-targeting ligands was developed in the last decades as an innovative therapeutic concept for Parkinson's disease (PD) and other neurodegenerative disorders. As the monoamine oxidase B (MAO B) and the histamine H3 receptor (H3 R) are promising targets for dopaminergic regulation, we synthetized dual-targeting ligands (DTLs) as non-dopaminergic receptor approach for the treatment of PD. Three series of compounds were developed by attaching the H3 R pharmacophore to indanone-related MAO B motifs, leading to development of MAO B/H3 R DTLs...
February 16, 2018: European Journal of Medicinal Chemistry
Dhaval R Kalaria, Mayank Singhal, Vandana Patravale, Virginia Merino, Yogeshvar N Kalia
Effective treatment of Parkinson's disease (PD) involves administration of therapeutic agents with complementary mechanisms of action in order to replenish, sustain or substitute endogenous dopamine. The objective of this study was to investigate anodal co-iontophoresis of pramipexole (PRAM; dopamine agonist) and rasagiline (RAS; MAO-B inhibitor) in vitro and in vivo. Passive permeation of PRAM and RAS (20 mM each) across porcine skin after 6 h was 15.7±1.9 and 16.0±2.9 µg/cm2 , respectively. Co-iontophoresis at 0...
February 22, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Dale E Edmondson, Claudia Binda
Monoamine oxidases A and B (MAO A and B) are mammalian flavoenzymes bound to the outer mitochondrial membrane. They were discovered almost a century ago and they have been the subject of many biochemical, structural and pharmacological investigations due to their central role in neurotransmitter metabolism. Currently, the treatment of Parkinson's disease involves the use of selective MAO B inhibitors such as rasagiline and safinamide. MAO inhibition was shown to exert a general neuroprotective effect as a result of the reduction of oxidative stress produced by these enzymes, which seems to be relevant also in non-neuronal contexts...
2018: Sub-cellular Biochemistry
Jun Hosogi, Rui Ohashi, Hiroshi Maeda, Kazuhiro Fujita, Junko Ushiki, Takashi Kuwabara, Yorihiro Yamamoto, Toru Imamura
We previously reported that KW-2449, (E)-1-{4-[2-(1H-Indazol-3-yl)vinyl]benzoyl}piperazine, a novel multikinase inhibitor developed for the treatment of leukemia patients, was oxidized to an iminium ion intermediate by monoamine oxidase B (MAO-B) and then converted to its oxo-piperazine form (M1) by aldehyde oxidase (AO). However, we found that the significant decrease in the pharmacologically active metabolite M1 following repeated administration of KW-2449 in primates might hamper the effectiveness of the drug...
February 16, 2018: Biopharmaceutics & Drug Disposition
Koichi Takao, Hideaki Yahagi, Yoshihiro Uesawa, Yoshiaki Sugita
A series of novel 3-(E)-styryl-2H-chromene derivatives were synthesized and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. All compounds exhibited no inhibitory activity towards MAO-A at 10 μM whereas compounds 1-5, 7, 9, 11-13, 15 and 16 showed strong inhibitory activity towards MAO-B at this concentration. Of these, compound 3, which contains fluorine at R 3 , showed the highest activity (IC 50 = 10 nM), and is about 22-fold more potent than pargyline (used as a positive control)...
February 7, 2018: Bioorganic Chemistry
Xiaoping Sun, Fangfang Zhu, Jun Zhou, Xiujuan Chang, Liang Li, Hanfei Hu, Zhenzhong Wang, Wei Xiao
BACKGROUND: Tianshu capsule(TSC)is a Chinese patent medicine. It's widely used to treat migraine clinically in China. AIM OF THE STUDY: In the present study, we investigated anti-migraine and anti-depression activities of TSC using in vivo animal models together with in vitro studies to investigate the mechanism of action. MATERIALS AND METHODS: Nitroglycerin (NTG) -induced migraine rat model, rat was given a subcutaneous injection of the NTG suspension (10 mg/kg) once a week for 5 weeks...
February 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Peter A LeWitt, Leo Verhagen Metman, Robert Rubens, Sarita Khanna, Sherron Kell, Suneel Gupta
OBJECTIVES: Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine)...
February 9, 2018: Clinical Neuropharmacology
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