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https://www.readbyqxmd.com/read/29438782/analgesic-effects-of-the-novel-semicarbazide-sensitive-amine-oxidase-inhibitor-szv-1287-in-mouse-pain-models-with-neuropathic-mechanisms-involvement-of-transient-receptor-potential-vanilloid-1-and-ankyrin-1-receptors
#1
Ádám Horváth, Valéria Tékus, Noémi Bencze, Nikolett Szentes, Bálint Scheich, Kata Bölcskei, Éva Szőke, Attila Mócsai, Éva Tóth-Sarudy, Péter Mátyus, Erika Pintér, Zsuzsanna Helyes
Semicarbazide-sensitive amine oxidase (SSAO) produces tissue irritants by deamination of primary amines, which activate transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors expressed predominantly on nociceptors. Since there are no data about its functions in pain, we studied the effects and mechanisms of action of our novel SSAO inhibitor and dual TRPA1/TRPV1 antagonist multi-target drug SZV 1287 in different pain models. Acute chemonociception was induced by TRPV1 and TRPA1 activation (resiniferatoxin and formalin, respectively), chronic arthritis by K/BxN serum transfer, traumatic mononeuropathy by sciatic nerve ligation...
February 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29425238/host-parasite-co-metabolic-activation-of-antitrypanosomal-aminomethyl-benzoxaboroles
#2
Ning Zhang, Martin Zoltner, Ka-Fai Leung, Paul Scullion, Sebastian Hutchinson, Ricardo C Del Pino, Isabel M Vincent, Yong-Kang Zhang, Yvonne R Freund, Michael R K Alley, Robert T Jacobs, Kevin D Read, Michael P Barrett, David Horn, Mark C Field
Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in Trypanosoma brucei...
February 9, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29408313/tmt-based-quantitative-proteomics-analysis-reveals-the-response-of-camellia-sinensis-to-fluoride
#3
Yanli Liu, Dan Cao, Linlong Ma, Xiaofang Jin, Pingfang Yang, Fei Ye, Panpan Liu, Ziming Gong, Chaoling Wei
The tea plant is a fluoride hyperaccumulator, and fluoride accumulation in its leaves is closely related to human health. To dissect molecular mechanisms underlying fluoride accumulation/detoxification, the leaves of tea seedlings exposed to different fluoride treatments for 30 days were sampled for physiological and proteomics analyses. The results showed that fluoride had no adverse effects on the growth of tea seedlings in spite of high content fluoride accumulation in their leaves. Through TMT coupled with UPLC MS/MS, 189 differentially accumulated proteins were quantified, of which 41 and 148 were localized in the cell wall and cellular compartments respectively...
February 2, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29400049/ratiometric-near-infrared-fluorescent-probe-for-synergistic-detection-of-monoamine-oxidase-b-and-its-contribution-to-oxidative-stress-in-cell-and-mice-aging-models
#4
Rui Wang, Xiaoyue Han, Jin-Mao You, Fabiao Yu, Lingxin Chen
As new biomarkers, monoamine oxidases (MAOs) play important roles in maintaining the homeostasis of biogenic amines via catalyzing the oxidation of biogenic amines to corresponding aldehydes with the generation of reactive oxygen species (ROS). MAOs have two isoforms, MAO-A and MAO-B. MAO-A is considered to be a major factor of neuropsychiatric and depressive disorders. However, MAO-B is thought to be involved in several neurodegenerative diseases. Therefore, to explore their distinct roles in different diseases, the selective detection of MAOs is essential...
February 5, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29392528/proteolytic-cleavage-of-vascular-adhesion-protein-1-induced-by-vascular-endothelial-growth-factor-in-retinal-capillary-endothelial-cells
#5
Shiho Yoshida, Miyuki Murata, Kousuke Noda, Takashi Matsuda, Michiyuki Saito, Wataru Saito, Atsuhiro Kanda, Susumu Ishida
PURPOSE: To investigate the mechanism of soluble vascular adhesion protein-1 (sVAP-1) accumulation induced by vascular endothelial growth factor (VEGF) in the vitreous of patients with diabetic retinopathy (DR). STUDY DESIGN: Experimental. METHODS: Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with proliferative diabetic retinopathy (PDR) with or without intravitreal bevacizumab (IVB) injection were determined by ELISA...
February 1, 2018: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29391504/mapping-the-interaction-site-and-effect-of-the-siglec-9-inflammatory-biomarker-on-human-primary-amine-oxidase
#6
Leonor Lopes de Carvalho, Heli Elovaara, Jerôme de Ruyck, Gerard Vergoten, Sirpa Jalkanen, Gabriela Guédez, Tiina A Salminen
Human primary amine oxidase (hAOC3), also known as vascular adhesion protein 1, mediates leukocyte rolling and trafficking to sites of inflammation by a multistep adhesion cascade. hAOC3 is absent on the endothelium of normal tissues and is kept upregulated during inflammatory conditions, which is an applicable advantage for imaging inflammatory diseases. Sialic acid binding immunoglobulin like-lectin 9 (Siglec-9) is a leukocyte ligand for hAOC3. The peptide (CARLSLSWRGLTLCPSK) based on the region of Siglec-9 that interacts with hAOC3, can be used as a specific tracer for hAOC3-targeted imaging of inflammation using Positron Emission Tomography (PET)...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29381339/structure-and-enzymatic-properties-of-an-unusual-cysteine-tryptophylquinone-dependent-glycine-oxidase-from-pseudoalteromonas-luteoviolacea
#7
Andres Andreo-Vidal, Kyle Mamounis, Esha Sehanobish, Dante Avalos, Jonatan Cristian Campillo-Brocal, Antonio Sanchez-Amat, Erik Thomas Yukl, Victor L Davidson
Glycine oxidase from Pseudoalteromonas luteoviolacea (PlGoxA) is a cysteine tryptophylquinone (CTQ)-dependent enzyme. Sequence and phylogenetic analysis place it in a newly designated subgroup (Group IID) of a recently identified family of LodA-like proteins, which are predicted to possess CTQ. The crystal structure of PlGoxA reveals that it is a homo-tetramer. It possesses an N-terminal domain with no close structural homologues in the Protein Data Bank. The active site is quite small due to inter-subunit interactions, which may account for the observed cooperativy towards glycine...
January 30, 2018: Biochemistry
https://www.readbyqxmd.com/read/29376208/halomonas-tabrizica-sp-nov-a-novel-moderately-halophilic-bacterium-isolated-from-urmia-lake-in-iran
#8
Sepideh Zununi Vahed, Haleh Forouhandeh, Vahideh Tarhriz, Nader Chaparzadeh, Mohammad Amin Hejazi, Che Ok Jeon, Mohammad Saeid Hejazi, Yunho Lee
A novel moderately halophilic, Gram-stain negative and aerobic bacterium, designated strain TBZ21T, was isolated from a water sample of Urmia Lake, Iran. Cells were observed to be non-motile rods with no flagellum, showing positive catalase and oxidase reactions. Strain TBZ21T was found to grow at 10-40 °C (optimum, 30 °C), at pH 7-10 (optimum, pH 8) and in the presence of 1-22% (optimum, 10%). The major fatty acids were identified as C19:0 cyclo ω8c, C16:0, Summed features 3 (C13:0 3-OH and/or iso-C15:1 H) and 8 (C18:1 ω7c and/or C18:1 ω6c) and C12:0 3-OH...
January 29, 2018: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/29367643/characterization-of-dopaminergic-system-in-the-striatum-of-young-adult-park2-knockout-rats
#9
Jickssa M Gemechu, Akhil Sharma, Dongyue Yu, Yuran Xie, Olivia M Merkel, Anna Moszczynska
Mutations in parkin gene (Park2) are linked to early-onset autosomal recessive Parkinson's disease (PD) and young-onset sporadic PD. Park2 knockout (PKO) rodents; however, do not display neurodegeneration of the nigrostriatal pathway, suggesting age-dependent compensatory changes. Our goal was to examine dopaminergic (DAergic) system in the striatum of 2 month-old PKO rats in order to characterize compensatory mechanisms that may have occurred within the system. The striata form wild type (WT) and PKO Long Evans male rats were assessed for the levels of DAergic markers, for monoamine oxidase (MAO) A and B activities and levels, and for the levels of their respective preferred substrates, serotonin (5-HT) and ß-phenylethylamine (ß-PEA)...
January 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29364582/a-genome-wide-scan-for-circulating-vascular-adhesion-protein-1-vap-1-levels-macrod2-as-a-potential-transcriptional-regulator-of-adipogenesis
#10
Yi-Cheng Chang, Siow-Wey Hee, Wei-Jei Lee, Hung-Yuan Li, Tien-Jyun Chang, Ming-Wei Lin, Yi-Jen Hung, I-Te Lee, Kuan-Yi Hung, Themistocles Assimes, Joshua W Knowles, Jiun-Yi Nong, Po-Chu Lee, Yen-Feng Chiu, Lee-Ming Chuang
AIM: Vascular adhesion protein-1 (VAP-1) is a membrane-bound amine oxidase highly expressed in mature adipocytes and is released into circulating. VAP-1 has been strongly implicated in several pathological process including diabetes, inflammation, hypertension, hepatic steatosis, and renal diseases and is an important disease marker and therapeutic target. Here we aimed to identify the genetic loci for circulating VAP-1 levels. METHODS: We conducted a genomic-wide linkage scan for the quantitative trait locus (QTL) of circulating VAP-1 levels in 1,100 Han Chinese subjects from 398 families in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study...
January 24, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29339289/characterization-of-two-extracellular-%C3%AE-glucosidases-produced-from-the-cellulolytic-fungus-aspergillus-sp-ydj216-and-their-potential-applications-for-the-hydrolysis-of-flavone-glycosides
#11
Jong Min Oh, Jae Pil Lee, Seung Cheol Baek, Seul Gi Kim, Yang Do Jo, Jungho Kim, Hoon Kim
A cellulolytic fungus YDJ216 was isolated from a compost and identified as an Aspergillus sp. strain. Two extracellular β-glucosidases, BGL1 and BGL2, were purified using ultrafiltration, ammonium sulfate fractionation, and High-Q chromatography. Molecular masses of BGL1 and BGL2 were estimated to be 97 and 45 kDa, respectively, by SDS-PAGE. The two enzymes eluted as one peak at 87 kDa by Sephacryl S-200 chromatography, and located at similar positions in a zymogram after intact gel electrophoresis, suggesting BGL1 and BGL2 might be monomeric and dimeric, respectively...
January 12, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29339253/design-synthesis-and-bioevalucation-of-novel-2-3-dihydro-1h-inden-1-amine-derivatives-as-potent-and-selective-human-monoamine-oxidase-b-inhibitors-based-on-rasagiline
#12
Xuan Xiao, Xing-Xing Zhang, Mei-Miao Zhan, Kai Cheng, Shiyu Li, Zhouling Xie, Chenzhong Liao
Parkinson's disease (PD) is associated with elevated levels of hMAO-B in the brain, and MAO-B has been recognized a successful target for developing anti-PD drugs. Herein we report rasagiline derivatives as novel potent and selective hMAO-B inhibitors. They were designed by employing fragment-based drug design strategy to link rasagiline and hydrophobic fragments, which may target a hydrophobic pocket in the entrance cavity of hMAO-B. Different linkers such as -OCH2-, -SCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2CH2O- were tried...
January 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29338223/chemo-enzymatic-synthesis-of-clickable-xylo-oligosaccharide-monomers-from-hardwood-4-o-methyl-glucuronoxylan
#13
Benjamin MacCormick, Thu V Vuong, Emma R Master
A chemo-enzymatic pathway was developed to transform 4-O-methylglucuronic acid (MeGlcpA) containing xylo-oligosaccharides from beechwood into clickable monomers capable of polymerizing at room temperature and in aqueous conditions to form unique polytriazoles. While the gluco-oligosaccharide oxidase (GOOX) from Sarocladium strictum was used to oxidize C6-propargylated oligosaccharides, the acid-amine coupling reagents EDAC and DMT-MM were employed and compared for their ability to append click functionalities to carboxylic acid groups of enzyme-treated oligosaccharides...
January 17, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29335210/privileged-scaffolds-as-mao-inhibitors-retrospect-and-prospects
#14
REVIEW
Avinash C Tripathi, Savita Upadhyay, Sarvesh Paliwal, Shailendra K Saraf
This review aims to be a comprehensive, authoritative, critical, and readable review of general interest to the medicinal chemistry community because it focuses on the pharmacological, chemical, structural and computational aspects of diverse chemical categories as monoamine oxidase inhibitors (MAOIs). Monoamine oxidases (MAOs), namely MAO-A and MAO-B represent an enormously valuable class of neuronal enzymes embodying neurobiological origin and functions, serving as potential therapeutic target in neuronal pharmacotherapy, and hence we have coined the term "Neurozymes" which is being introduced for the first time ever...
January 4, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29301981/controlling-of-n-alkylpolyamine-analogue-metabolism-by-selective-deuteration
#15
Sebahat Ucal, Merja R Häkkinen, Aino-Liisa Alanne, Leena Alhonen, Jouko Vepsäläinen, Tuomo A Keinänen, Mervi T Hyvönen
Replacing protium with deuterium is an efficient method to modulate drug metabolism. N -alkylated polyamine analogues are polyamine antimetabolites with proven anticancer efficacy. We have characterized earlier the preferred metabolic routes of N1,N12 -diethylspermine (DESpm), N1 -benzyl- N12 -ethylspermine (BnEtSpm) and N1,N12 -dibenzylspermine (DBSpm) by human recombinant spermine oxidase (SMOX) and acetylpolyamine oxidase (APAO). Here we studied the above analogues, their variably deuterated counterparts and their metabolites as substrates and inhibitors of APAO, SMOX, semicarbazide-sensitive amine oxidase (SSAO), diamine oxidase (DAO) and monoamine oxidases...
January 4, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29261141/evaluation-of-the-expression-of-amine-oxidase-proteins-in-breast-cancer
#16
Woo Young Sun, Junjeong Choi, Yoon Jin Cha, Ja Seung Koo
We aimed to evaluate the expression of amine oxidase proteins in breast cancer and their clinical implications. We performed immunohistochemical staining of amine oxidase proteins (LOX, lysyl oxidase, AOC3, amine oxidase, MAOA, monoamine oxidase A, MAOB, monoamine oxidase B). Based on their hormone receptors, such as estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 immunohistochemical staining, breast cancer was divided into four molecular subtypes: luminal A, luminal B, HER-2 type, and triple-negative breast cancer (TNBC)...
December 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29247860/structure-activity-studies-on-n-substituted-tranylcypromine-derivatives-lead-to-selective-inhibitors-of-lysine-specific-demethylase-1-lsd1-and-potent-inducers-of-leukemic-cell-differentiation
#17
Johannes Schulz-Fincke, Mirjam Hau, Jessica Barth, Dina Robaa, Dominica Willmann, Andreas Kürner, Julian Haas, Gabriele Greve, Tinka Haydn, Simone Fulda, Michael Lübbert, Steffen Lüdeke, Tobias Berg, Wolfgang Sippl, Roland Schüle, Manfred Jung
FAD-dependent lysine-specific demethylase 1 (LSD1) is overexpressed or deregulated in many cancers such as AML and prostate cancer and hence is a promising anticancer target with first inhibitors in clinical trials. Clinical candidates are N-substituted derivatives of the dual LSD1-/monoamine oxidase-inhibitor tranylcypromine (2-PCPA) with a basic amine function in the N-substituent. These derivatives are selective over monoamine oxidases. So far, only very limited information on structure-activity studies about this important class of LSD1 inhibitors is published in peer reviewed journals...
December 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29243863/synthesis-and-antioxidant-antixanthine-oxidase-and-antielastase-activities-of-novel-n-s-substituted-polyhalogenated-nitrobutadiene-derivatives
#18
Nihal Onul, Onur Ertik, Nese Mermer, Refiye Yanardag
In this study, three substituted polyhalogenated nitrobutadiene derivatives were synthesized. Compound 1-[(2,3-dibromopropyl)sulfanyl]-1,3,4,4-tetrachloro-2-nitrobuta-1,3-diene (4) was synthesized before by our group. Compounds 8-{[1-[(2,3-dibromopropyl)sulfany]-3,4,4-trichloro-2-nitrobuta-1,3-butadien-1-yl}-1,4-dioxa-8-azaspiro[4.5]decane (5) and 1-[(2,3-dibromopropyl)sulfanyl]-3,4,4-trichloro-N-(4-methylpiperazin-1-yl)-2-nitrobuta-1,3-diene-1-amine (6) were synthesized in this work as original compounds. Xanthine oxidase, elastase inhibition abilities, and antioxidant activities were investigated in this work for compounds 4, 5, and 6...
December 15, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29198609/synthesis-and-evaluation-of-biaryl-derivatives-for-structural-characterization-of-selective-monoamine-oxidase-b-inhibitors-toward-parkinson-s-disease-therapy
#19
Seul Ki Yeon, Ji Won Choi, Jong-Hyun Park, Ye Rim Lee, Hyeon Jeong Kim, Su Jeong Shin, Bo Ko Jang, Siwon Kim, Yong-Sun Bahn, Gyoonhee Han, Yong Sup Lee, Ae Nim Pae, Ki Duk Park
Benzyloxyphenyl moiety is a common structure of highly potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and sembragiline. We synthesized 4-(benzyloxy)phenyl and biphenyl-4-yl derivatives including halogen substituents on the terminal aryl unit. In addition, we modified the carbon linker between amine group and the biaryl linked unit. Among synthesized compounds, 12c exhibited the most potent and selective MAO-B inhibitory effect (hMAO-B IC50: 8.9 nM; >10,000-fold selectivity over MAO-A) as a competitive inhibitor...
November 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29193544/characterisation-of-a-bacterial-galactokinase-with-high-activity-and-broad-substrate-tolerance-for-chemoenzymatic-synthesis-of-6-aminogalactose-1-phosphate-and-analogues
#20
Kun Huang, Fabio Parmeggiani, Edward Pallister, Chuen-Jiuan Huang, Fang-Fang Liu, Qian Li, William R Birmingham, Peter Both, Baptiste Thomas, Li Liu, Josef Voglmeir, Sabine Flitsch
Glycosyl phosphates are important intermediates in many metabolic pathways and are substrates for diverse carbohydrate active enzymes. There is a need to develop libraries of structurally similar analogues that can be used as selective chemical probes in glycomics. Here we explore chemoenzymatic cascades for the fast generation of glycosyl phosphate libraries without protecting group strategies. The key enzyme is a new bacterial galactokinase (LgGalK) cloned from Leminorella grimontii which was produced in E...
November 29, 2017: Chembiochem: a European Journal of Chemical Biology
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