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https://www.readbyqxmd.com/read/28097900/structure-activity-relationships-of-fraxamoside-as-an-unusual-xanthine-oxidase-inhibitor
#1
Rosa Maria Vitale, Lina Antenucci, Margherita Gavagnin, Gennaro Raimo, Pietro Amodeo
Fraxamoside, a macrocyclic secoiridoid glucoside featuring a hydroxytyrosol group, was recently identified as a xanthine oxidase inhibitor (XOI) comparable in potency in vitro to the standard antigout drug allopurinol. However, this activity and its considerably higher value than its derivatives oleuropein, oleoside 11-methyl ester, and hydroxytyrosol are not explained by structure-activity relationships (SARs) of known XOIs. To exclude allosteric mechanisms, we first determined the inhibition kinetic of fraxamoside...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28097880/practical-applications-of-matched-series-analysis-sar-transfer-binding-mode-suggestion-and-data-point-validation
#2
Peter Hunt, Matthew Segall, Noel O'Boyle, Roger Sayle
AIM: The assumption in scaffold hopping is that changing the scaffold does not change the binding mode and the same structure-activity relationships (SARs) are seen for substituents decorating each scaffold. Results/methodology: We present the use of matched series analysis, an extension of matched molecular pair analysis, to automate the analysis of a project's data and detect the presence or absence of comparable SAR between chemical series. CONCLUSION: The presence of SAR transfer can confirm the perceived binding mode overlay of different chemotypes or suggest new arrangements between scaffolds that may have gone unnoticed...
January 18, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28094938/in-vitro-and-in-vivo-evaluation-of-fully-substituted-5-3-ethoxy-3-oxopropynyl-4-ethoxycarbonyl-1-2-3-triazolyl-glycosides-as-original-nucleoside-analogs-to-circumvent-resistance-in-myeloid-malignancies
#3
Hella Amdouni, Guillaume Robert, Mohsine Driowya, Nathan Furstoss, Camille Métier, Alix Dubois, Maeva Dufies, Marwa Zerhouni, François Orange, Sandra Lacas-Gervais, Khalid Bougrin, Anthony R Martin, Patrick Auberger, Rachid Benhida
A series of nucleoside analogs bearing a 1,4,5-trisubstituted-1,2,3-triazole aglycone was synthesized using a straightforward click/electrophilic addition or click/oxidative coupling tandem procedures. SAR analysis, using cell culture assays, led to the discovery of a series of compounds belonging to the 5-alkynyl-1,2,3-triazole family that exhibits potent antileukemic effects on several hematologic malignancies including chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) either sensitive or resistant to their respective therapy...
January 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28094524/antimalarial-pyrido-1-2-a-benzimidazoles-lead-optimization-parasite-life-cycle-stage-profile-mechanistic-evaluation-killing-kinetics-and-in-vivo-oral-efficacy-in-a-mouse-model
#4
Kawaljit Singh, John Okombo, Christel Brunschwig, Ferdinand Ndubi, Linley Barnard, Chad Wilkinson, Peter M Njogu, Mathew Njoroge, Lizahn Laing, Marta Machado, Miguel Prudêncio, Janette Reader, Mariette E Botha, Sindisiwe H Nondaba, Lyn-Marie Birkholtz, Sonja Lauterbach, Alisje Churchyard, Theresa L Coetzer, Jeremy N Burrows, Clive Leonard Yeates, Paolo Denti, Lubbe Wiesner, Timothy J Egan, Sergio Wittlin, Kelly Chibale
Further structure activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials, have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of haemozoin formation possibly contributes to the mechanism of action.
January 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28094221/synthesis-biological-evaluation-and-molecular-docking-analysis-of-2-phenyl-benzofuran-3-carboxamide-derivatives-as-potential-inhibitors-of-staphylococcus-aureus-sortase-a
#5
Wan He, Yong Zhang, Jian Bao, Xinxian Deng, Jennifer Batara, Shawn Casey, Qiuyuan Guo, Faqin Jiang, Lei Fu
In Gram-positive bacteria, Sortase A (Srt A) is a critical cysteine transpeptidase that is responsible for recognizing and assembling surface virulence proteins through the recognition of a LPXTG (leucine, proline, X, threonine, and glycine, where X is any amino acid) signal. Mutants lacking genes for Srt A attenuate infections without affecting microbial viability. Here a series of 2-phenyl-benzofuran-3-carboxamide derivatives were synthesized and identified as potent Srt A inhibitors. Activity assays revealed that multiple compounds exhibited excellent inhibitory activity against Srt A compared with known Sortase A inhibitor pHMB (IC50=130μM)...
December 25, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28094220/molecular-docking-discovery-synthesis-and-pharmacological-properties-of-new-6-substituted-2-3-phenoxyphenyl-4-phenyl-quinoline-derivatives-an-approach-to-developing-potent-dna-gyrase-inhibitors-antibacterial-agents
#6
Manikandan Alagumuthu, Sivakumar Arumugam
Synthesis and molecular validation of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives (4a-h) as antibacterial/DNA gyrase inhibitors reported. Primarily, 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives were docked into the active sites of DNA gyrase A&B, to ensure the binding mode of the compounds, and the results were superior on DNA gyrase A over DNA gyrase B. Based on this, S. aureus DNA gyrase A assay was proposed and executed. Most prominent DNA gyrase inhibition showed by 6-fluoro-2-(3-phenoxyphenyl)-4-phenylquinoline (4c), IC50 0...
January 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28093976/chemoinformatics-profiling-of-the-chromone-nucleus-as-a-mao-b-a2aar-dual-binding-scaffold
#7
Maykel Cruz-Monteagudo, Fernanda Borges, M Natália D S Cordeiroc, Aliuska Morales Helguerad, Eduardo Tejerab, Cesar Paz-Y-Miñob, Aminael Sánchez-Rodrígueze, Yunier Perera-Sardiñaf, Yunierkis Perez-Castillo
BACKGROUND: In the context of the current drug discovery efforts to find disease modifying therapies for Parkinson´s disease (PD) the current single target strategy has proved inefficient. Consequently, the search for multi-potent agents is attracting more and more attention due to the multiple pathogenetic factors implicated in PD. Multiple evidences points to the dual inhibition of the monoamine oxidase B (MAO-B), as well as adenosine A2A receptor (A2AAR) blockade, as a promising approach to prevent the neurodegeneration involved in PD...
January 16, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28093893/arabidopsis-thaliana-glutathione-s-transferase-theta-2-interacts-with-rsi1-fld-to-activate-systemic-acquired-resistance
#8
Zeeshan Zahoor Banday, Ashis Kumar Nandi
A partly infected plant develops systemic acquired resistance (SAR) and shows heightened resistance during subsequent infections. The infected parts generate certain mobile signals that travel to the distal tissues and help in activation of SAR. SAR is associated with epigenetic modifications of several defense-related genes. However, the mechanisms by which mobile signals contribute to epigenetic changes are little known. Previously we had shown that the Arabidopsis REDUCED SYSTEMIC IMMUNITY 1 (RSI1, alias FLOWERING LOCUS D; FLD), which codes for a putative histone demethylase is required for the activation of SAR...
January 17, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28089701/functionalized-triazines-as-potent-hcv-entry-inhibitors
#9
Eric S Mull, Li-Qiang Sun, Qian Zhao, Betsy Eggers, Kevin Pokornowski, Guangzhi Zhai, Ramkumar Rajamani, Susan Jenkins, Melissa Kramer, Ying-Kai Wang, Hua Fang, Daniel Tenney, Carl J Baldick, Mark I Cockett, Nicholas A Meanwell, Paul M Scola
A series of potent and novel acylsulfonamide-bearing triazines were synthesized and the structure-activity relationships (SARs) as HCV entry inhibitors were evaluated. This acylsulfonamide series was derived from an early lead, 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoic acid wherein the carboxylic acid was replaced with an acylsulfonamide moiety. This structural modification provided a class of compounds which projected an additional vector off the terminus of the acylsulfonamide functionality as a means to drive activity...
December 18, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28089699/investigation-of-piperazine-benzamides-as-human-%C3%AE-3-adrenergic-receptor-agonists-for-the-treatment-of-overactive-bladder
#10
Bart H Harper, Liping Wang, Cheng Zhu, Nam F Kar, Bing Li, Christopher R Moyes, Stephen D Goble, Melissa Costa, Karen Dingley, Jerry Di Salvo, Sookhee N Ha, Amanda Hurley, Xiaofang Li, Randy R Miller, Hiroshi Nagabukuro, Gino M Salituro, Sean Smith, Mary Struthers, Jeffrey J Hale, Scott D Edmondson, Richard Berger
The synthesis of a novel class of piperazine benzamide (reverse amides) targeting the human β3-adrenergic receptor for the treatment of overactive bladder (OAB) is described. The SAR studies directed towards maintaining well established β3 potency and selectivities while improving the overall pharmacokinetic profile in the reverse amide class will be evaluated. The results and consequences associated with functional activity at the norepinephrine transporter (NET) will also be discussed.
December 11, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28088901/advanced-structure-activity-relationships-applied-to-mentha-spicata-l-subsp-spicata-essential-oil-compounds-as-ache-and-nmda-ligands-in-comparison-with-donepezil-galantamine-and-memantine-new-approach-in-brain-disorders-pharmacology
#11
Speranta Avram, Mernea Maria, Eyup Bagci, Lucian Hritcu, Livia-Cristina Borcan, Dan Mihailescu
BACKGROUND: Alzheimer's disease (AD) therapy is based on several natural and synthetic compounds that act as acetylcholinesterase (AChE) and N-methyl-D-aspartate receptor (NMDA) ligands that have limited efficiency in relieving AD symptoms. Recent studies show that inhibitors isolated from Mentha spicata L. subsp. spicata are promising for AD therapy. OBJECTIVE: We aimed to identify novel and more potent phytopharmaceutical compounds for AD treatment by taking into account the compounds from Mentha spicata L...
January 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28078535/tubulin-polymerization-stimulating-activity-of-ganoderma-triterpenoids
#12
Toshitaka Kohno, Tran Hai-Bang, Qinchang Zhu, Yhiya Amen, Seiichi Sakamoto, Hiroyuki Tanaka, Satoshi Morimoto, Kuniyoshi Shimizu
Tubulin polymerization is an important target for anticancer therapies. Even though the potential of Ganoderma triterpenoids against various cancer targets had been well documented, studies on their tubulin polymerization-stimulating activity are scarce. This study was conducted to evaluate the effect of Ganoderma triterpenoids on tubulin polymerization. A total of twenty-four compounds were investigated using an in vitro tubulin polymerization assay. Results showed that most of the studied triterpenoids exhibited microtuble-stabilizing activity to different degrees...
January 11, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28077633/surveillance-of-bat-coronaviruses-in-kenya-identifies-relatives-of-human-coronaviruses-nl63-and-229e-and-their-recombination-history
#13
Ying Tao, Mang Shi, Christina Chommanard, Krista Queen, Jing Zhang, Wanda Markotter, Ivan V Kuzmin, Edward C Holmes, Suxiang Tong
: Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya during 2007-2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the break-point located near 5' and 3' end of the spike (S) protein gene...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076824/discovery-of-new-nanomolar-inhibitors-of-gpa-extension-of-2-oxo-1-2-dihydropyridinyl-3-yl-amide-based-gpa-inhibitors
#14
Wendy A Loughlin, Ian D Jenkins, N David Karis, Peter C Healy
Glycogen Phosphorylase (GP) is a functionally active dimeric enzyme, which is a target for inhibition of the conversion of glycogen to glucose-1-phosphate. In this study we report the design and synthesis of 14 new pyridone derivatives, and seek to extend the SAR analysis of these compounds. The SAR revealed the minor influence of the amide group, importance of the pyridone ring both spatially around the pyridine ring and for possible π-stacking, and confirmed a preference for inclusion of 3,4-dichlorobenzyl moieties, as bookends to the pyridone scaffold...
December 26, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28075367/high-performance-anti-retransmission-deception-jamming-utilizing-range-direction-multiple-input-and-multiple-output-mimo-synthetic-aperture-radar-sar
#15
Ruijia Wang, Jie Chen, Xing Wang, Bing Sun
Retransmission deception jamming seriously degrades the Synthetic Aperture Radar (SAR) detection efficiency and can mislead SAR image interpretation by forming false targets. In order to suppress retransmission deception jamming, this paper proposes a novel multiple input and multiple output (MIMO) SAR structure range direction MIMO SAR, whose multiple channel antennas are vertical to the azimuth. First, based on the multiple channels of range direction MIMO SAR, the orthogonal frequency division multiplexing (OFDM) linear frequency modulation (LFM) signal was adopted as the transmission signal of each channel, which is defined as a sub-band signal...
January 9, 2017: Sensors
https://www.readbyqxmd.com/read/28075343/a-fast-synthetic-aperture-radar-raw-data-simulation-using-cloud-computing
#16
Zhixin Li, Dandan Su, Haijiang Zhu, Wei Li, Fan Zhang, Ruirui Li
Synthetic Aperture Radar (SAR) raw data simulation is a fundamental problem in radar system design and imaging algorithm research. The growth of surveying swath and resolution results in a significant increase in data volume and simulation period, which can be considered to be a comprehensive data intensive and computing intensive issue. Although several high performance computing (HPC) methods have demonstrated their potential for accelerating simulation, the input/output (I/O) bottleneck of huge raw data has not been eased...
January 8, 2017: Sensors
https://www.readbyqxmd.com/read/28074203/multitopic-ligand-directed-assembly-of-low-dimensional-metal-chalcogenide-organic-frameworks
#17
Yi Liu, Kaiqi Ye, Yue Wang, Qichun Zhang, Xianhui Bu, Pingyun Feng
Despite tremendous progress in metal-organic frameworks, only limited success has been achieved with metal-chalcogenide organic frameworks. Metal-chalcogenide organic frameworks are desirable because they offer a promising route towards tunable semiconducting porous frameworks. Here, four novel semiconducting chalcogenide-organic hybrid compounds have been synthesized through a solvothermal method. Multitopic organic molecules, i.e., 1,2-di-(4-pyridyl)ethylene (L(1)), 1,3,5-tris(4-pyridyl-trans-ethenyl)benzene (L(2)) and tetrakis(4-pyridyloxymethylene)methane (L(3)), have been used as linkers to assemble Zn(SAr)2 or Zn2(SAr)4 units to generate different patterns of spatial organizations...
January 11, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28073672/the-long-story-of-camptothecin-from-traditional-medicine-to-drugs
#18
REVIEW
Emanuela Martino, Serena Della Volpe, Elisa Terribile, Emanuele Benetti, Mirena Sakaj, Adriana Centamore, Andrea Sala, Simona Collina
20-(S)-Camptothecin (CPT) is a natural alkaloid extracted from the bark of Camptotheca acuminata (Chinese happy tree). It acts as a DNA topoisomerase 1 poison with an interesting antitumor activity and its use is limited by low stability and solubility and unpredictable drug-drug interactions. Since the late 20th century, it has been widely used in cancer therapy and, since extraction yields from plant tissues are very low, various synthetic routes have been developed to satisfy the increase in demand for CPT...
December 31, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28072461/adverse-and-beneficial-effects-in-chinese-hamster-lung-fibroblast-cells-following-radiofrequency-exposure
#19
Anna Sannino, Olga Zeni, Stefania Romeo, Rita Massa, Maria Rosaria Scarfi
In this study, the effect of radiofrequency (RF) exposure to 1950 MHz, Universal Mobile Telecommunication System signal, was investigated in Chinese hamster lung fibroblast cell line (V79). Genotoxic and cytotoxic effects of 20-h exposure at specific absorption rate (SAR) values from 0.15 W/kg to 1.25 W/kg were measured by means of cytokinesis-block micronucleus (MN) assay. Exposure was carried out blinded under strictly controlled conditions of dosimetry and temperature. The effect of RF exposure alone at four SAR values was tested, that is, 0...
January 10, 2017: Bioelectromagnetics
https://www.readbyqxmd.com/read/28067996/virtual-screening-sar-and-discovery-of-5-indole-3-yl-2-2-nitrophenyl-amino-1-3-4-oxadiazole-as-a-novel-bcl-2-inhibitor
#20
Noha I Ziedan, Rania Hamdy, Alessandra Cavaliere, Malamati Kourti, Filippo Prencipe, Andrea Brancale, Arwyn T Jones, Andrew D Westwell
A new series of oxadiazoles were designed to act as inhibitors of the anti-apoptotic Bcl-2 protein. Virtual screening led to the discovery of new hits that interact with Bcl-2 at the BH3 binding pocket. Further study of the structure-activity relationship of the most active compound of the first series, compound 1, led to the discovery of a novel oxadiazole analogue, compound 16j, that was a more potent small molecule inhibitor of Bcl-2. 16j had good in vitro inhibitory activity with sub-micromolar IC50 values in a metastatic human breast cancer cell line (MDA-MB-231) and a human cervical cancer cell line (HeLa)...
January 9, 2017: Chemical Biology & Drug Design
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