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https://www.readbyqxmd.com/read/28927796/development-and-evaluation-of-4-pyrrolidin-3-yl-benzonitrile-derivatives-as-inhibitors-of-lysine-specific-demethylase-1
#1
Daniel P Mould, Ulf Bremberg, Allan M Jordan, Matthis Geitmann, Alison E McGonagle, Tim C P Somervaille, Gary J Spencer, Donald J Ogilvie
As part of our ongoing efforts to develop reversible inhibitors of LSD1, we identified a series of 4-(pyrrolidin-3-yl)benzonitrile derivatives that act as successful scaffold-hops of the literature inhibitor GSK-690. The most active compound, 21g, demonstrated a Kd value of 22nM and a biochemical IC50 of 57nM. In addition, this compound displayed improved selectivity over the hERG ion channel compared to GSK-690, and no activity against the related enzymes MAO-A and B. In human THP-1 acute myeloid leukaemia cells, 21g was found to increase the expression of the surrogate cellular biomarker CD86...
August 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28916252/decreased-monoamine-oxidase-a-expression-and-activity-in-the-bladders-of-rats-with-partial-outlet-obstruction
#2
Mai Michishita, Kazuo Yano, Ken-Ichi Tomita, Satoru Yoshikawa, Osamu Matsuzaki, Ken-Ichi Kasahara
OBJECTIVE To investigate changes in expression and activity of monoamine oxidase A (MAO-A) in rats with partial bladder outlet obstruction (pBOO). Previous studies suggested that monoamines, such as serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (NA), are involved in bladder hyperactivity secondary to pBOO. However, little is known about the role of MAO-A, an enzyme oxidizing 5-HT and NA, in the pathogenesis. METHODS Female Sprague Dawley rats were subjected to sham or pBOO operations for 7 days, then their bladders were isolated...
September 12, 2017: Urology
https://www.readbyqxmd.com/read/28882179/medical-expenditure-for-esophageal-cancer-in-china-a-10-year-multicenter-retrospective-survey-2002-2011
#3
Lan-Wei Guo, Hui-Yao Huang, Ju-Fang Shi, Li-Hong Lv, Ya-Na Bai, A-Yan Mao, Xian-Zhen Liao, Guo-Xiang Liu, Jian-Song Ren, Xiao-Jie Sun, Xin-Yu Zhu, Jin-Yi Zhou, Ji-Yong Gong, Qi Zhou, Lin Zhu, Yu-Qin Liu, Bing-Bing Song, Ling-Bin Du, Xiao-Jing Xing, Pei-An Lou, Xiao-Hua Sun, Xiao Qi, Shou-Ling Wu, Rong Cao, Li Lan, Ying Ren, Kai Zhang, Jie He, Jian-Gong Zhang, Min Dai
BACKGROUND: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. METHODS: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China...
September 7, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28862601/-comparative-analysis-of-expression-of-genes-encoding-enzymes-of-catecholamine-catabolism-and-renalase-in-tissues-of-normotensive-and-hypertensive-rats
#4
V I Fedchenko, A E Medvedev
Comparative analysis of expression of genes encoding enzymes of catecholamine catabolism (monoaminbe oxidases A and B (MAO A and MAO B) and catechol-O-methyl transferase (COMT)) and renalase has been carried out in tissues of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Among investigated tissues the highest level of mRNA of genes encoding key enzymes of catecholamine catabolism (MAO A, MAO B, COMT) was found in the heart of WKY rats. In SHR the mRNA levels of these genes were lower (p<0...
July 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28857544/identification-of-5-1-methyl-5-trifluoromethyl-1h-pyrazol-3-yl-thiophene-2-carboxamides-as-novel-and-selective-monoamine-oxidase-b-inhibitors-used-to-improve-memory-and-cognition
#5
Alan P Kaplan, Terence Keenan, Roderick Scott, Xianbo Zhou, Rusiko Bourchouladze, Andrew J McRiner, Mark E Wilson, Darlene Romashko, Regina Miller, Matthew Bletsch, Gary Anderson, Jennifer Stanley, Adia Zhang, Dong Lee, John Nikpur
Initial work in Drosophila and mice demonstrated that the transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) is a master control gene for memory formation. The relationship between CREB and memory has also been found to be true in other species, including aplysia and rats. It is thus well-established that CREB activation plays a central role in memory enhancement and that CREB is activated during memory formation. On the basis of these findings, a phenotypic high-throughput screening campaign utilizing a CRE-luciferase (CRE-Luci) SK-N-MC cell line was performed to identify compounds that enhance transcriptional activation of the CRE promoter with a suboptimal dose of forskolin...
September 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28851912/association-of-monoamine-oxidase-a-genetic-variants-and-amygdala-morphology-in-violent-offenders-with-antisocial-personality-disorder-and-high-psychopathic-traits
#6
Nathan J Kolla, Raihaan Patel, Jeffrey H Meyer, M Mallar Chakravarty
Violent offending is elevated among individuals with antisocial personality disorder (ASPD) and high psychopathic traits (PP). Morphological abnormalities of the amygdala and orbitofrontal cortex (OFC) are present in violent offenders, which may relate to the violence enacted by ASPD + PP. Among healthy males, monoamine oxidase-A (MAO-A) genetic variants linked to low in vitro transcription (MAOA-L) are associated with structural abnormalities of the amygdala and OFC. However, it is currently unknown whether amygdala and OFC morphology in ASPD relate to MAO-A genetic polymorphisms...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839357/using-molecular-docking-analysis-to-discovery-dregea-sinensis-hemsl-potential-mechanism-of-anticancer-antidepression-and-immunoregulation
#7
Xiujie Liu, Yu Shi, Yulin Deng, Rongji Dai
BACKGROUND: Dregea sinensis Hemsl. plant of the genus Dregea volubilis (Asclepiadaceae), plays a vital role in anticancer, antidepression, and immunoregulation. Steroidal glycosides are the main constituents of this herb, which were significant biological active ingredients. OBJECTIVE: The objective of this study is to recognize the mechanism of anticancer, antidepression, and immunoregulation of D. sinensis Hemsl. MATERIALS AND METHODS: Seventy-two steroidal glycosides of D...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28836294/how-fast-monoamine-oxidases-decompose-adrenaline-kinetics-of-isoenzymes-a-and-b-evaluated-by-empirical-valence-bond-simulation
#8
Gabriel Oanca, Jernej Stare, Janez Mavri
This work scrutinizes kinetics of decomposition of adrenaline catalyzed by monoamine oxidase (MAO) A and B enzymes, a process controlling the levels of adrenaline in the central nervous system and other tissues. Experimental kinetic data for MAO A and B catalyzed decomposition of adrenaline are reported only in the form of the maximum reaction rate. Therefore we estimated the experimental free energy barriers form the kinetic data of closely related systems using regression method, as was done in our previous study...
August 24, 2017: Proteins
https://www.readbyqxmd.com/read/28828994/computational-chemistry-study-of-natural-alkaloids-and-homemade-databank-to-predict-inhibitory-potential-against-key-enzymes-in-neurodegenerative-disease
#9
Vitor Prates Lorenzo, Mateus Feitosa Alves, Luciana Scotti, Sócrates Golzio Dos Santos, Margareth de Fátima Formiga Melo Diniz, Marcus Tullius Scotti
Cissampelos sympodialis Eichl is used in folk medicine for the treatment of various inflammatory diseases; several alkaloids were isolated from this species and some of them have anti-allergic activity, immunomodulatory and spasmolytic. Treatment of rats with the total tertiary alkaloid fraction showed an antidepressant effect. One of the depression causes can be the deficiency of monoamines, which is a factor displayed in patients with Alzheimer's disease. Theoretical studies using in silico methods have aided in the process of drug discovery...
August 21, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28825626/pharmacological-and-toxicological-screening-of-novel-benzimidazole-morpholine-derivatives-as-dual-acting-inhibitors
#10
Nafiz Öncü Can, Ulviye Acar Çevik, Begüm Nurpelin Sağlık, Yusuf Özkay, Özlem Atlı, Merve Baysal, Ümide Demir Özkay, Özgür Devrim Can
The aim of this study was to investigate acetylcholinesterase (AChE), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibitory, and antimicrobial activities of a new series of 2-(4-substituted phenyl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzimidazole derivatives, for their possible use as multi-action therapeutic agents. Target compounds (n = 15) were synthesized under microwave irradiation conditions in two steps, and their structures were elucidated by FT-IR, ¹H-NMR, (13)C-NMR and high resolution mass spectroscopic analyses...
August 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28814861/the-influence-of-direct-laser-metal-sintering-implants-on-the-early-stages-of-osseointegration-in-diabetic-mini-pigs
#11
Naiwen Tan, Xiangwei Liu, Yanhui Cai, Sijia Zhang, Bo Jian, Yuchao Zhou, Xiaoru Xu, Shuai Ren, Hongbo Wei, Yingliang Song
BACKGROUND: High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models. METHODS: Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28797883/design-synthesis-and-biological-evaluation-of-novel-coumarin-n-benzyl-pyridinium-hybrids-as-multi-target-agents-for-the-treatment-of-alzheimer-s-disease
#12
Jin-Shuai Lan, Yue Ding, Yun Liu, Ping Kang, Jian-Wei Hou, Xin-Yu Zhang, Sai-Sai Xie, Tong Zhang
Combining N-benzyl pyridinium moiety and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activities were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for ChE and Aβ (1-42) self-aggregation, and clearly selective inhibition to MAO-B over MAO-A. Of these compounds, compound 7f was the most potent inhibitor for hMAO-B, and it was also a good and balanced inhibitor to ChEs and hMAO-B (0.0373 μM for eeAChE; 2...
July 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28794929/high-frequency-direct-shoot-organogenesis-of-leaf-explants-and-a-comparative-evaluation-of-phytochemicals-antioxidant-potential-of-wild-vs-in-vitro-plant-extracts-of-lysimachia-laxa
#13
Sanjoy Gupta, Tapan Seal, A A Mao, Soneswar Sarma
The present studies were attempted to develop direct shoot organogenesis from in vitro grown leaf explants of Lysimachia laxa and comparative evaluation of phytochemical and antioxidant potential of in vitro raised and wild plants extracts. The fresh leaves of this species are used for deworming gastrointestinal worm infection in traditional medicine. Overexploitation of this species and poor regeneration has led to rapid decline in wild population, therefore, present investigation was attempted to develop an efficient rapid mass propagation protocol for this species...
August 2017: 3 Biotech
https://www.readbyqxmd.com/read/28762173/methylene-blue-and-its-analogues-as-antidepressant-compounds
#14
REVIEW
Anzelle Delport, Brian H Harvey, Anél Petzer, Jacobus P Petzer
Methylene Blue (MB) is considered to have diverse medical applications and is a well-described treatment for methemoglobinemias and ifosfamide-induced encephalopathy. In recent years the focus has shifted to MB as an antimalarial agent and as a potential treatment for neurodegenerative disorders such as Alzheimer's disease. Of interest are reports that MB possesses antidepressant and anxiolytic activity in pre-clinical models and has shown promise in clinical trials for schizophrenia and bipolar disorder. MB is a noteworthy inhibitor of monoamine oxidase A (MAO-A), which is a well-established target for antidepressant action...
July 31, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28753408/contribution-of-monoamine-oxidases-to-vascular-oxidative-stress-in-patients-with-end-stage-renal-disease-requiring-hemodialysis
#15
Diana Utu, Stelian Pantea, Oana M Duicu, Danina M Muntean, Adrian Sturza
Arteriovenous fistula (AVF) is the 'life line' for patients with end-stage renal disease (ESRD) undergoing hemodialysis. AVF maturation failure is a poorly understood process, one of the contributors being endothelial dysfunction due to oxidative stress. Monoamine oxidases (MAOs) A and B were recently identified as novel sources of vascular oxidative stress. The aim of the present study was to assess the contribution of MAOs to the endothelial dysfunction in patients with ESDR with indication of hemodialysis...
July 28, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28742414/neural-correlates-of-depressive-symptoms-in-smokers-a-systematic-review-of-imaging-studies
#16
Michele de Oliveira Gonzalez, Anna E Goudriaan, Cíntia de Azevedo-Marques Périco, Marcela Waisman Campos, Arthur Guerra de Andrade, Dinesh Bhugra, João Mauricio Castaldelli-Maia
This review aims to summarize neuroimaging studies in order to better understand the neural correlates of depressive symptoms in tobacco smokers. Using the keywords "depressive OR depression" AND "tobacco OR nicotine OR smok(*) OR cigarette" AND "neuroimage OR magnetic resonance OR smri OR structural magnetic resonance OR fmri OR functional magnetic resonance OR pet OR positron emission tomography", literature search was conducted in PubMed, Web of Science and PsycINFO databases. The first and the last author read the abstracts of all the studies found in the search (n = 179)...
July 25, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28738332/neuroprogression-and-immune-activation-in-major-depressive-disorder
#17
Jeffrey H Meyer
Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28728104/design-synthesis-and-evaluation-of-coumarin-pargyline-hybrids-as-novel-dual-inhibitors-of-monoamine-oxidases-and-amyloid-%C3%AE-aggregation-for-the-treatment-of-alzheimer-s-disease
#18
Hua-Li Yang, Pei Cai, Qiao-Hong Liu, Xue-Lian Yang, Fan Li, Jin Wang, Jia-Jia Wu, Xiao-Bing Wang, Ling-Yi Kong
A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC50, 0.027 ± 0.004 μM for MAO-B; 3.275 ± 0.040 μM for MAO-A) and Aβ1-42 aggregation (54.0 ± 1.1%, 25 μM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test...
July 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28705604/major-depression-and-heart-failure-interest-of-monoamine-oxidase-inhibitors
#19
REVIEW
Sophie Corbineau, Marie Breton, Jeanne Mialet-Perez, Jean-François Costemale-Lacoste
Several physiopathological hypotheses have been studied to explain the link between heart failure (HF) and major depression (MD). An increase of monoamine oxidase (MAO) has recently been found as a factor involved in the development of HF. The aim of this review is to provide a complete overview of the involvement of MAOs in HF comorbidity of MD and to discuss the pharmacological options. Our work highlights the scientific evidence of MAO involvement in the development of HF. Studies focusing on MAO-A seem to have reproducible results on HF, establishing the effect of this enzyme as well as the protective effect of its inhibition...
July 8, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28700656/unexpected-effects-of-azole-transporter-inhibitors-on-antifungal-susceptibility-in-candida-glabrata-and-other-pathogenic-candida-species
#20
Yohsuke Nagayoshi, Taiga Miyazaki, Shintaro Shimamura, Hironobu Nakayama, Asuka Minematsu, Shunsuke Yamauchi, Takahiro Takazono, Shigeki Nakamura, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae, Koichi Izumikawa
The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C...
2017: PloS One
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