journal
MENU ▼
Read by QxMD icon Read
search

ACS Chemical Neuroscience

journal
https://www.readbyqxmd.com/read/27806195/development-of-new-positron-emission-tomography-radiotracer-for-bet-imaging
#1
Changning Wang, Frederick A Schroeder, Jacob M Hooker
The bromodomain and extra-terminal domain (BET) inhibitors have been extensively studied for tumor treatment in the past few years. Recently, BET-containing proteins have been reported to play a key role in brain functions, such as learning and memory. BET proteins have also been shown to be a potential therapeutic target for substance abuse disorders. Development of a molecular probe for non-invasive imaging will elucidate the distribution and functional roles of BET in the living subject and accelerate medical research and drug discovery in this domain...
November 2, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27806193/neuroprotective-effect-of-a-new-7-8-dihydroxycoumarin-based-fe2-cu2-chelator-in-cell-and-animal-models-of-parkinson-s-disease
#2
Pabla Aguirre, Olimpo García-Beltrán, Victoria Tapia, Yorka Muñoz, Bruce Kennedy Cassels, Marco T Nunez
Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ ̴ Fe2+ > Zn2+ > Fe3+...
November 2, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27805811/selective-small-molecule-activators-of-trek-2-channels-stimulate-drg-c-fiber-nociceptor-k2p-currents-and-limit-calcium-influx
#3
Prassana K Dadi, Nicholas Catin Vierra, Emily L Days, Matthew Dickerson, Paige N Vinson, C David Weaver, David A Jacobson
The two-pore-domain potassium (K2P) channel TREK-2 serves to modulate plasma membrane potential in dorsal root ganglia c-fiber nociceptors, which tunes electrical excitability and nociception. Thus, TREK-2 activators are considered a potential therapeutic target for treating pain; however, there are currently no selective pharmacological tools for TREK-2 channels. Here we report the identification of the first TREK-2 selective activators using a high-throughput fluorescence-based thallium (Tl(+)) flux screen (HTS)...
November 2, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27801563/functional-characterization-of-a-novel-series-of-biased-signaling-dopamine-d3-receptor-agonists
#4
Wei Xu, Xiaozhao Wang, Aaron M Tocker, Peng Huang, Maarten E A Reith, Lee-Yuan Liu-Chen, Amos B Smith Iii, Sandhya Kortagere
Dopamine receptors play an integral role in controlling brain physiology. Importantly sub-type selective agonists and antagonists of dopamine receptors with biased signaling properties have been successful in treating psychiatric disorders with a low incidence of side effects. To this end, we recently designed and developed SK609, a dopamine D3 receptor (D3R) selective agonist that has atypical signaling properties. SK609 has shown efficacy in reversing akinesia and reducing L-dopa-induced dyskinesia in a hemiparkinsonian rats...
November 1, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27797173/dipeptidyl-vinyl-sulfone-as-a-novel-chemical-tool-to-inhibit-hmgb1-nlrp3-inflammasome-and-inflamma-mirs-in-a%C3%AE-mediated-microglial-inflammation
#5
Ana Sofia Falcão, Luís A R Carvalho, Gonçalo Lidónio, Ana Rita Vaz, Susana Dias Lucas, Rui Moreira, Dora Brites
Rapid microglial activation and associated inflammatory pathways contribute to immune-defense and tissue repair in the central nervous system (CNS). However, persistent activation of these cells will ultimately result in vast production of pro-inflammatory mediators and other neurotoxic factors, which may induce neuronal damage and contribute to chronic neurodegenerative diseases, as Alzheimer's disease (AD). Therefore, small molecules with immunomodulatory effects on microglia may be considered as potential tools to counteract their pro-inflammatory phenotype and neuroimmune dysregulation in such disorders...
October 31, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27797168/dual-inhibition-of-pdk1-and-aurora-kinase-a-an-effective-strategy-to-induce-differentiation-and-apoptosis-of-human-glioblastoma-multiforme-stem-cells
#6
Simona Daniele, Simona Sestito, Deborah Pietrobono, Chiara Giacomelli, Grazia Chiellini, Danilo Di Maio, Luciana Marinelli, Ettore Novellino, Claudia Martini, Simona Rapposelli
The poor prognosis of Glioblastoma Multiforme (GBM) is mainly attributed to drug resistance mechanisms and to the existence of a subpopulation of glioma stem cells (GSCs). Multi-target compounds able to both affect different deregulated pathways and the GSC subpopulation could escape tumour resistance, and most importantly, eradicate the stem cell reservoir. In this respect, the simultaneous inhibition of Phosphoinositide-dependent kinase-1 (PDK1) and Aurora Kinase A (AurA), each one playing a pivotal role in cellular survival/migration/differentiation, could represent an innovative strategy to overcome GBM resistance and recurrence...
October 31, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27792315/nuclear-overhauser-enhancement-mediated-magnetization-transfer-imaging-in-glioma-with-different-progression-at-7-t
#7
Xiangyong Tang, Zhuozhi Dai, Gang Xiao, Gen Yan, Zhiwei Shen, Tao Zhang, Guishan Zhang, Zerui Zhuang, Yuanyu Shen, Zhiyan Zhang, Wei Hu, Renhua Wu
Glioma is a malignant neoplasm affecting the central nervous system. The conventional approaches to diagnosis, such as T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced T1WI, give an oversimplified representation of anatomic structures. Nuclear Overhauser enhancement (NOE) imaging is a special form of magnetization transfer (MT) that provides a new way to detect small solute pools through indirect measurement of attenuated water signals, and makes it possible to probe semi-solid macromolecular protons...
October 28, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27776205/investigations-on-16-arylideno-steroids-as-a-new-class-of-neuroprotective-agents-for-the-treatment-of-alzheimer-s-and-parkinson-s-diseases
#8
Ranjit Singh, Ranju Bansal
Neuroinflammatory mechanisms mediated by activated glial and cytokines (TNF-α, IL-1β) might contribute neuronal degeneration leading to Alzheimer's (AD) and Parkinson's disease (PD). Lipopolysaccharide (LPS) is an inflammogen derived from the cell wall of Gram-negative bacteria, which promotes neuroinflammation and subsequent neurodegeneration. Dehydroepiandrosterone (DHEA) and testosterone have been reported as neuroprotective steroids useful for the treatment of various neurodegenerative disorders. In the present study, several 16-arylidene steroidal derivatives have been evaluated as neuroprotective agents in LPS-treated animal models...
October 24, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27762555/synthesis-of-gly-%C3%AE-z-cf-ch-phe-a-fluoroalkene-dipeptide-isostere-and-its-incorporation-into-a-leu-enkephalin-peptidomimetic
#9
Jean-Francois Nadon, Kristina Rochon, Sébastien Grastilleur, Guillaume Langlois, Thi Thanh Hà Dao, Véronique Blais, Brigitte Guérin, Louis Gendron, Yves L Dory
A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the third peptide bond has been prepared and studied. This new analog is produced by replacing the third amide of Leu-enkephalin with a fluoroalkene. An efficient and innovative synthesis of the corresponding dipeptide surrogate Fmoc-Gly-Ψ[(Z)CF=CH]-Phe-OH is described. The key step involves the alkylation of a tin dienolate from the less hindered face of its chiral sulfonamide auxiliary derived from camphor. Once its synthesis was complete, its incorporation into the peptidomimetic sequence was achieved on a solid support with chlorotrityl resin and following the Fmoc strategy...
October 20, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27744679/identification-of-the-first-marine-derived-opioid-receptor-balanced-agonist-with-a-signaling-profile-that-resembles-the-endorphins
#10
Tyler A Johnson, Laura Milan-Lobo, Tao Che, Madeline Ferwerda, Eptisam Lambo, Nicole L McIntosh, Fei Li, Li He, Nicholas Lorig-Roach, Phillip Crews, Jennifer Lynne Whistler
Opioid therapeutics are excellent analgesics, whose utility is compromised by dependence. Morphine (1) and its clinically relevant derivatives such as OxyContin® (4), Vicodin® (5) and Dilaudid® (6) are "biased" agonists at the µ opioid receptor (OR), wherein they engage G-protein signaling but poorly engage β-arrestin and the endocytic machinery. In contrast, the endorphins, met-enkephalin (14) and β-endorphin (15), endogenous peptide agonists for ORs, are more potent analgesics then 1, show reduced liability for tolerance and dependence, and engage both G-protein and β-arrestin pathways as "balanced" agonists...
October 17, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27744678/discovery-of-indazoles-as-potent-orally-active-dual-neurokinin-1-receptor-antagonists-and-serotonin-transporter-inhibitors-for-the-treatment-of-depression
#11
Andrew P Degnan, George O Tora, Hong Huang, David A Conlon, Carl D Davis, Umesh M Hanumegowda, Xiaoping Hou, Yi Hsiao, Joanna Hu, Rudolph Krause, Yu-Wen Li, Amy E Newton, Rick L Pieschl, Joseph Raybon, Thorsten Rosner, Jung-Hui Sun, Matthew T Taber, Sarah J Taylor, Michael K Wong, Huiping Zhang, Nicholas J Lodge, Joanne J Bronson, John E Macor, Kevin W Gillman
Combination studies of neurokinin 1 (NK1) receptor antagonists and serotonin-selective reuptake inhibitors (SSRIs) have shown promise in preclinical models of depression. Such a combination may offer important advantages over the current standard of care. Herein we describe the discovery and optimization of an indazole-based chemotype to provide a series of potent dual NK1 receptor antagonists/serotonin transporter (SERT) inhibitors to overcome issues of ion channel blockade. This effort culminated in the identification of compound 9, an analog that demonstrated favorable oral bioavailability, excellent brain uptake, and robust in vivo efficacy in a validated depression model...
October 17, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27741398/a-fluorine-18-labeled-antagonist-for-pet-imaging-of-kappa-opioid-receptors
#12
Zhengxin Cai, Song Ye Li, Richard Pracitto, Antonio Navarro, Anupama Shirali, Jim Ropchan, Yiyun Henry Huang
Kappa opioid receptor (KOR) antagonists are potential drug candidates for diseases such as treatment-refractory depression, anxiety, and addictive disorders. PET imaging radiotracers for KOR can be used in occupancy study to facilitate drug development, and to investigate the roles of KOR in health and diseases. We have previously developed two 11C-labeled antagonist radiotracers with high affinity and selectivity toward KOR. What is limiting their wide applications is the short half-life of 11C. Herein, we report the synthesis of a first 18F-labeled KOR antagonist radiotracer and the initial PET imaging study in a non-human primate...
October 14, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27741392/tempo-technically-extended-multiparameter-optimization-an-advanced-robust-scoring-scheme-to-calculate-central-nervous-system-cns-druggability-and-monitor-lead-optimization
#13
Arup K Ghose, Gregory R Ott, Robert L Hudkins
At the drug discovery stage, it is important to understand the design concepts of a CNS drug compared to a non-CNS drug. Previously we published on ideal CNS drug space and defined in detail the physicochemical property space distribution of CNS and non-CNS oral drugs, the application of radar charting (a graphical representation of multiple physicochemical properties used during CNS lead optimization) and a recursive partition classification tree to differentiate between CNS and non-CNS drugs. The objective of the present study was to further the understanding of differentiations between CNS and non-CNS oral drugs into the development and application of an effective CNS algorithm TEMPO (Technically Extended Multiparameter Optimization)...
October 14, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27739675/new-modalities-in-drug-therapy-modifying-ongoing-chemical-conversations-in-the-brain
#14
Terry Kenakin
The modification of ongoing chemical signaling in the brain through allosteric modification of seven transmembrane receptors offers a wealth of diverse beneficial outcomes in drug therapy. Specifically, biased agonism can emphasize beneficial signals and de-emphasize harmful signals thus increasing the effectiveness of agonists and opening up new vistas for previously precluded drug targets. In addition, the modification of natural agonism through positive and negative allostery can provide useful rejuvenation of failing systems...
October 14, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27736095/meeting-the-challenge-using-cytological-profiling-to-discover-chemical-probes-from-traditional-chinese-medicines-against-parkinson-s-disease
#15
Chao Wang, Xinzhou Yang, George D Mellick, Yunjiang Feng
Parkinson's disease (PD) is an incurable neurodegenerative disorder with a high prevalence rate worldwide. The fact that there are currently no proven disease-modifying treatments for PD underscores the urgency for a more comprehensive understanding of the underlying disease mechanism. Chemical probes have been proven to be powerful tools for studying biological processes. Traditional Chinese medicine (TCM) contains a huge reservoir of bioactive small molecules as potential chemical probes that may hold the key to unlocking the mystery of PD biology...
October 13, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27736094/brain-hyperglycemia-induced-by-heroin-association-with-metabolic-neural-activation
#16
Ernesto Solis, R Aaron Bola, Bradley J Fasulo, Eugene A Kiyatkin
Glucose enters the brain extracellular space from arterial blood and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (~150-200 μM or ~15-25% over resting baseline)...
October 13, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27731637/effect-of-oleracein-e-a-neuroprotective-tetrahydroisoquinoline-on-rotenone-induced-parkinson-s-disease-cell-and-animal-models
#17
Hongxiang Sun, Xiuquan He, Cejia Liu, Lingyu Li, Ruoyu Zhou, Tianyun Jin, Su Yue, Da Feng, Jie Gong, Jiawei Sun, Jianbo Ji, Lan Xiang
Oleracein E (OE), a tetrahydroisoquinoline possessing potent anti-oxidant activity, was first isolated from a traditional Chinese medicine, Portulaca oleraea L., and is hypothesized to be a neuroprotectant. In the present study, we evaluated the effects of racemic OE on rotenone-induced toxicity in Parkinson's disease (PD) cell and animal models. Pre-treatment with OE (10 μM, 2 h) decreased LDH release and the apoptosis rate in rotenone (5 μM, 24 h)-treated SH-SY5Y human neuroblastoma cells. Further mechanistic study indicated that OE reduced reactive oxygen species (ROS) levels, inhibited ERK1/2 phosphorylation, reduced rotenone-induced up-regulation of the proapoptotic protein Bax, and prevented cytochrome C release and caspase-3 activation...
October 12, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27731633/ith14001-a-cgp37157-nimodipine-hybrid-designed-to-regulate-calcium-homeostasis-and-oxidative-stress-exerts-neuroprotection-in-cerebral-ischemia
#18
Izaskun Buendia, Giammarco Tenti, Patrycja Michalska, Iago Méndez-López, Enrique Luengo, Michele Satriani, Juan Fernando Padin Nogueira, Manuela G López, María Teresa Ramos, Antonio G García, J Carlos Menéndez, Rafael León
During brain ischemia, oxygen and glucose deprivation induces calcium overload, extensive oxidative stress, neuroinflammation and, finally, massive neuronal loss. In the search of a neuroprotective compound to mitigate this neuronal loss, we have designed and synthesized a new multitarget hybrid (ITH14001) directed at the reduction of calcium overload by acting on two regulators of calcium homeostasis; the mitochondrial Na+/Ca2+ exchanger (mNCX) and L-type voltage dependent calcium channels (VDCCs). This compound is a hybrid of CGP37157 (mNCX inhibitor) and nimodipine (L-type VDCCs blocker), and its pharmacological evaluation revealed a moderate ability to selectively inhibit both targets...
October 12, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27726337/synthesis-nicotinic-acetylcholine-receptor-binding-in-vitro-and-in-vivo-pharmacological-properties-of-2-fluoro-substituted-thiophenyl-deschloroepibatidine-analogs
#19
Pauline W Ondachi, Ana H Castro, Benjamin Sherman, Charles W Luetje, M Imad Damaj, Samuel Wayne Mascarella, Hernán A Navarro, Frank Ivy Carroll
The synthesis, nAChR in vitro and in vivo pharmacological properties of 2'-fluoro-3'-(substituted thiophenyl)deschloroepibatidine analogues (5a-f, 6a-d, and 7a-c) are presented herein. All had subnanomolar affinity at α4β2*-nAChRs. Contrary to lead structure epibatidine, a potent nAChR agonist, all were potent α4β2- and α3β4-AChR antagonists in an in vitro functional assay. In vivo, the compounds were also nAChR antagonists with various degrees of agonist activity. Compounds 5e, 5f, 6a, 6c, 6d, and 7c had no agonist effects in the tail-flick, hot-plate, hypothermia, or spontaneous activity tests whereas 5a-d, 7a and 7b did not have agonist activity in the tail-flick and hot-plate tests but like varenicline, were agonists in the hypothermia and spontaneous activity tests...
October 11, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27665765/targeting-gliomas-can-a-new-alkylating-hybrid-compound-make-a-difference
#20
Rui Pinheiro, Cláudia Braga, Gisela Santos, Maria R Bronze, Maria J Perry, Rui Moreira, Dora Brites, Ana S Falcão
Glioblastoma (GBM) is the most common and aggressive type of brain tumor in adults. The triazene Temozolomide (TMZ), an alkylating drug, is the classical chemotherapeutic agent for gliomas, but has been disappointing against the highly invasive and resistant nature of GBM. Hybrid compounds may open new horizons within this challenge. The multicomponent therapeutic strategy here used resides on a combination of two repurposing drugs acting by different but potentially synergistic mechanisms, improved efficacy, and lower resistance effects...
October 11, 2016: ACS Chemical Neuroscience
journal
journal
42896
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"