The Experts below are selected from a list of 329121 Experts worldwide ranked by ideXlab platform
V F Zarytova - One of the best experts on this subject based on the ideXlab platform.
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Composites of Peptide Nucleic Acids with Titanium Dioxide Nanoparticles. IV+. Antiviral Activity of Nanocomposites Containing DNA/PNA Duplexes
Russian Journal of Bioorganic Chemistry, 2015Co-Authors: R N Amirkhanov, N A Mazurkova, N V Amirkhanov, V F ZarytovaAbstract:Antiviral activity of TiO2 · PL · DNA/PNA nanobiocomposites was studied on the MDCK cell culture infected with influenza A virus (H3N2 subtype). A PNA fragment in nanocomposites was electrostatically bound in the form of a DNA/PNA heteroduplex to titanium dioxide nanoparticles precovered with polylysine (TiO2 · PL). It was shown that TiO2 · PL · DNA1/PNA1 nanobiocomposite bearing the PNA1 fragment targeted to the 3′-end of the noncoding region of segment 5 of viral RNA specifically inhibited the virus reproduction with an efficiency of 99.8%. The 50% cytotoxic concentration (TC50) and 50% effective inhibitory concentration (IC50) of the TiO2 · PL · DNA1/PNA1 nanocomposite were evaluated to be more than 1200 μg/mL and less than 3 μg/mL, respectively. Based on these data, the selectivity index (SI) for TiO2 · PL · DNA1/PNA1 nanobiocomposite defined as the TC50/IC50 ratio, was calculated to be more than 400. Thus, TiO2 · PL · DNA/PNA nanobiocomposites were shown to not only penetrate through cell membranes, but exhibit a high specific antisense activity without toxic effects on the living cells.
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Composites of Peptide Nucleic Acids with Titanium Dioxide Nanoparticles. IV+. Antiviral Activity of Nanocomposites Containing DNA/PNA Duplexes
Bioorganicheskaia khimiia, 2015Co-Authors: R N Amirkhanov, N A Mazurkova, N V Amirkhanov, V F ZarytovaAbstract:Antiviral activity of TiO2 · PL · DNA/PNA nanobiocomposites was studied on the MDCK cell culture infected with influenza A virus (subtype H3N2). PNA fragment in nanocomposites as a DNA/PNA heteroduplex is electrostatically bound to titanium dioxide nanoparticles precovered with polylysine (TiO2 · PL). It was shown that TiO2 · PL · DNA1/PNA1 nanobiocomposit bearing PNA1 fragment targeted to the 3'-end of the noncoding region of segment 5 of viral RNA specifically inhibited the virus reproduction with the efficiency of 99.8%. It was determined that the 50% cytotoxic concentration (TC50) of the TiO2 · PL · DNA1/PNA1 nanocomposite is more than 1200 mg/mL. And 50% effective inhibitory concentration (IC50) is less than 0.003 mg/mL. Based on these data, the selectivity index (SI) for TiO2 · PL · DNA1/PNA1 nanobiocomposite defined as the ratio TC50/LC50, is more than 400. Thus TiO2 · PL · DNA/PNA nanobiocomposites can not only penatrate through cell membrane, but and are able to exhibit a high specific antisense activity, without causing toxic effects on the living cells.
Xiao Min - One of the best experts on this subject based on the ideXlab platform.
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Effect of Tanreqing injection on anti-respiratory syncytial virus(RSV,long strain) in vitro
2011Co-Authors: Xiao MinAbstract:Objective To explore anti-respiratory syncytial virus(RSV) effect of Chinese medicinal Tanreqing injection.Methods The technique of cell cultuer and MTT with ribavirin as positive concentration-dependent manner.Results The median toxic concentration(TC50) of 3.972 g/L in Hep-2 cell culture.The median effective concentration(EC50)was 0.428 g/L when drug was added 24h before infection,the EC50 was 1.160g/L when drug was added 2 h after virus infection,and it was 1.189 g/L as the drug was added after it mixed with virus 24 h.The therapeutic index(TI)was 9.28,3.42and 3.34 respectively.Conclusions Tanreqing injection has the direct deactivation and blocking effect on RSV.The preventive effect is the most evident with the same concentration in vitro.
Sara Mckellip - One of the best experts on this subject based on the ideXlab platform.
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Development of (E)-2-((1,4-dimethylpiperazin-2-ylidene)amino)-5-nitro-N-phenylbenzamide, ML336: Novel 2-amidinophenylbenzamides as potent inhibitors of venezuelan equine encephalitis virus.
Journal of Medicinal Chemistry, 2014Co-Authors: Chad E. Schroeder, Julie Sotsky, Nichole A. Tower, James W. Noah, Robert A Smith, Sara MckellipAbstract:Venezuelan equine encephalitis virus (VEEV) is an emerging pathogenic alphavirus that can cause significant disease in humans. Given the absence of therapeutic options available and the significance of VEEV as a weaponized agent, an optimization effort was initiated around a quinazolinone screening hit 1 with promising cellular antiviral activity (EC50 = 0.8 μM), limited cytotoxic liability (CC50 > 50 μM), and modest in vitro efficacy in reducing viral progeny (63-fold at 5 μM). Scaffold optimization revealed a novel rearrangement affording amidines, specifically compound 45, which was found to potently inhibit several VEEV strains in the low nanomolar range without cytotoxicity (EC50 = 0.02–0.04 μM, CC50 > 50 μM) while limiting in vitro viral replication (EC90 = 0.17 μM). Brain exposure was observed in mice with 45. Significant protection was observed in VEEV-infected mice at 5 mg kg–1 day–1 and viral replication appeared to be inhibited through interference of viral nonstructural proteins.
Huang Xiaoju - One of the best experts on this subject based on the ideXlab platform.
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A Study on Inhibiting Effects of Plantago Asiatica on Respiratory Syncytial Virus in Vitro
Journal of Hubei University for Nationalities, 2015Co-Authors: Huang XiaojuAbstract:Objective To study the effects of anti-respiratory syncytial virus( RSV) with Plantago asiatica.Methods The antiviral activity of Plantago asiatica extract was tested by the technique of cell culture,with ribavirin as the positive control. Virus cytopathic effect( CPE) was used to measure half toxic concentration( TC50),half inhibitive concentration( IC50) and therapeutic index( TI).Results Plantago asiatica inhibited RSV infection in dose-effect relationship. Its TC50,IC50,TI were 4.57 g /L,0.285 g /L,16.04 respectively.Plantago asiatica had small toxicity,large antiviral index and security range The anti-RSV role was similar to the same dose of ribavirin. Conclusion Plantago asiatica has a significant anti-RSV effect in vitro.
Povl Krogsgaard-larsen - One of the best experts on this subject based on the ideXlab platform.
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Structural Determinants of AMPA Agonist Activity in Analogues of 2-Amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic Acid: Synthesis and Pharmacology
Journal of Medicinal Chemistry, 2000Co-Authors: Benny Bang-andersen, Tine B. Stensbøl, Sibylle Moltzen Lenz, Haleh Ahmadian, Klaus Peter Bogeso, Ulf Madsen, Povl Krogsgaard-larsenAbstract:We have previously shown that the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA, 2), binds to AMPA receptors in a manner different from that of AMPA (1) itself and that 2, in contrast to 1, also binds to kainic acid receptor sites. To elucidate the structural requirements for selective activation of the site/conformation of AMPA receptors recognized by 2, a number of isosteric analogues of 2 have now been synthesized and pharmacologically characterized. The compound 2-amino-3-(5-carboxy-3-methoxy-4-isoxazolyl)propionic acid (3a) (IC50 = 0.11 μM; EC50 = 1.2 μM), which is a regioisostere of 2 with a methoxy group substituted for the methyl group, was approximately equipotent with 2 (IC50 = 0.020 μM; EC50 = 1.0 μM) as an inhibitor of [3H]AMPA binding and as an AMPA agonist, respectively, whereas the corresponding 3-ethoxy analogue 3b (IC50 = 1.0 μM; EC50 = 4.8 μM) was slightly weaker. The analogues 3c−e, cont...
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AMPA receptor agonists: resolution, configurational assignment, and pharmacology of (+)-(S)- and (-)-(R)-2-amino-3-[3-hydroxy-5-(2-pyridyl)-isoxazol-4-yl]-propionic acid (2-Py-AMPA).
Chirality, 1997Co-Authors: Tommy N Johansen, Bjarke Ebert, Erik Falch, Povl Krogsgaard-larsenAbstract:We have previously shown that whereas (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA) shows the characteristics of a partial agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, (S)-APPA is a full AMPA receptor agonist and (R)-APPA a weak competitive AMPA receptor antagonist. This observation led us to introduce the new pharmacological concept, functional partial agonism. Recently we have shown that the 2-pyridyl analogue of APPA, (RS)-2-amino-3-[3-hydroxy-5-(2-pyridyl)isoxazol-4-yl]propionic acid (2-Py-AMPA), is a potent and apparently full AMPA receptor agonist, and this compound has now been resolved into (+)- and (-)-2-Py-AMPA (ee > or = 99.0%) by chiral HPLC using a Chirobiotic T column. The absolute stereochemistry of the enantiomers of APPA has previously been established by X-ray analysis, and on the basis of comparative studies of the circular dichroism spectra of the enantiomers of APPA and 2-Py-AMPA, (+)- and (-)-2-Py-AMPA were assigned the (S)- and (R)-configuration, respectively. In a series of receptor binding studies, neither enantiomer of 2-Py-AMPA showed detectable affinity for kainic acid receptor sites or different sites at the N-methyl-D-aspartic acid (NMDA) receptor complex. (+)-(S)-2-Py-AMPA was an effective inhibitor of [3H]AMPA binding (IC50 = 0.19 +/- 0.06 microM) and a potent AMPA receptor agonist in the rat cortical wedge preparation (EC50 = 4.5 +/- 0.3 microM) comparable with AMPA (IC50 = 0.040 +/- 0.01 microM; EC50 = 3.5 +/- 0.2 microM), but much more potent than (+)-(S)-APPA (IC50 = 5.5 +/- 2.2 microM; EC50 = 230 +/- 12 microM). Like (-)-(R)-APPA (IC50 > 100 microM), (-)-(R)-2-Py-AMPA (IC50 > 100 microM) did not significantly affect [3H]AMPA binding, and both compounds were weak AMPA receptor antagonists (Ki = 270 +/- 50 and 290 +/- 20 microM, respectively).
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AMPA Receptor Agonists: Synthesis, Protolytic Properties, and Pharmacology of 3-Isothiazolol Bioisosteres of Glutamic Acid
Journal of Medicinal Chemistry, 1997Co-Authors: Lisa Matzen, Anne Engesgaard, Povl Krogsgaard-larsen, Bjarke Ebert, Bente Frølund, Michael Didriksen, Jerzy W. JaroszewskiAbstract:A number of 3-isothiazolol bioisosteres of glutamic acid (1) and analogs of the AMPA receptor agonist, (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA, 2a), including (RS)-2-amino-3-(3-hydroxy-5-methylisothiazol-4-yl)propionic acid (thio-AMPA, 2b), were synthesized. Comparative in vitro pharmacological studies on this series of 3-isothiazolol and the corresponding 3-isoxazolol amino acids were performed using a series of receptor binding assays (IC50 values) and the electrophysiological rat cortical slice model (EC50 values). Whereas 2a (IC50 = 0.04 ± 0.005 μM, EC50 = 3.5 ± 0.2 μM) is markedly more potent than the tert-butyl analog ATPA (3a) (IC50 = 2.1 ± 0.16 μM, EC50 = 34 ± 2.4 μM) in [3H]AMPA binding and electrophysiological studies, 2b (IC50 = 1.8 ± 0.13 μM, EC50 = 15.0 ± 2.4 μM) was approximately equipotent with thio-ATPA (3b) (IC50 = 0.63 ± 0.07 μM, EC50 = 14 ± 1.3 μM). (RS)-2-Amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (HIBO, 4a) was approximately equipotent with its thio an...
