Styryl-Based and Tricyclic Compounds as Potential Anti-Prion Agents
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{"title"=>"Styryl-based and tricyclic compounds as potential anti-prion agents", "type"=>"journal", "authors"=>[{"first_name"=>"Erika", "last_name"=>"Chung", "scopus_author_id"=>"36611348100"}, {"first_name"=>"Frances", "last_name"=>"Prelli", "scopus_author_id"=>"7003535919"}, {"first_name"=>"Stephen", "last_name"=>"Dealler", "scopus_author_id"=>"7006260883"}, {"first_name"=>"Woo Sirl", "last_name"=>"Lee", "scopus_author_id"=>"35741194600"}, {"first_name"=>"Young Tae", "last_name"=>"Chang", "scopus_author_id"=>"54790563500"}, {"first_name"=>"Thomas", "last_name"=>"Wisniewski", "scopus_author_id"=>"7005291375"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"21931860", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0024844", "pui"=>"362555454", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "scopus"=>"2-s2.0-80052821738", "sgr"=>"80052821738"}, "id"=>"f48b4e0e-c914-3e86-9206-fe85fca56db0", "abstract"=>"Prion diseases currently have no effective therapy. These illnesses affect both animal and human populations, and are characterized by the conformational change of a normal self protein PrP(C) (C for cellular) to a pathological and infectious conformer, PrP(Sc) (Sc for scrapie). We used a well characterized tissue culture model of prion infection, where mouse neuroblastoma cells (N2a) were infected with 22L PrP(Sc), to screen compounds for anti-prion activity. In a prior study we designed a library of styryl based, potential imaging compounds which were selected for high affinity binding to Alzheimer's disease beta-amyloid plaques and good blood-brain barrier permeability. In the current study we screened this library for activity in the N2a/22L tissue culture system. We also tested the anti-prion activity of two clinically used drugs, trimipramine and fluphenazine, in the N2a/22L system. These were selected based on their structural similarity to quinacrine, which was previously reported to have anti-prion activity. All the compounds were also screened for toxicity in tissue culture and their ability to disaggregate amyloid fibrils composed of PrP and beta-amyloid synthetic peptides in vitro. Two of the imaging agents, 23I and 59, were found to be both effective at inhibiting prion infection in N2a/22L tissue culture and to be non-toxic. These two compounds, as well as trimipramine and fluphenazine were evaluated in vivo using wild-type CD-1 mice infected peripherally with 139A PrP(Sc). All four agents significantly prolonged the asymptomatic incubation period of prion infection (p<0.0001 log-rank test), as well as significantly reducing the degree of spongiform change, astrocytosis and PrP(Sc) levels in the brains of treated mice. These four compounds can be considered, with further development, as candidates for prion therapy.", "link"=>"http://www.mendeley.com/research/styrylbased-tricyclic-compounds-potential-antiprion-agents", "reader_count"=>31, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>6, "Student > Ph. D. Student"=>9, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>6, "Student > Ph. D. Student"=>9, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>6, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Chemistry"=>6, "Psychology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>6}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "Lithuania"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/736474"], "description"=>"<p>PrP<sup>Sc</sup> level in the spleen at 60 dpi. At this time, there is peripheral replication of PrP<sup>Sc</sup> but CNS invasion has not yet occurred. Spleen homogenates for each group (n = 10) were tested for levels of PrP<sup>Sc</sup> and plotted with the vehicle level represented as 100% infectivity. Differences between each treated group versus the control group were not significant.</p>", "links"=>[], "tags"=>["geriatrics", "molecular biology", "microbiology", "neuroscience", "pharmacology", "pathology", "neurological disorders", "Non-clinical medicine", "Infectious diseases"], "article_id"=>406814, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g007", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Level_of_PrP_Sc_in_the_Spleen_/406814", "title"=>"Level of PrP<sup>Sc</sup> in the Spleen.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:53:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/736718"], "description"=>"<p>Spongiform density. Spongiform change in the basal ganglia of all groups were quantified using Bioquant NovaPrime image analysis. Histological sections were stained with cresyl violet. A,B) Represent a section of basal ganglia of non-treated control animals at 25× and 100× magnification respectively. C,D) Represent a treatment group (fluphenazine) at 25× and 100× magnification. Arrows are highlighting vacuoles representing spongiform change. E) Bar graph representation of spongiform density quantification of all animal groups. Graphs were plotted as percent spongiform change per area. All treatment groups had significantly lower levels of spongiform density compared to non-treated control; ***<i>p</i><0.0001 by One-way ANOVA; *<i>p</i><0.05 Newman-Keuls <i>post-hoc</i> analysis versus N2a/22L as indicated on the graph.</p>", "links"=>[], "tags"=>["spongiform"], "article_id"=>407067, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g009", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitation_of_Spongiform_Change_/407067", "title"=>"Quantitation of Spongiform Change.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:57:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/736056"], "description"=>"<p>Cytotoxicity of compounds. A) Fluphenazine B) trimipramine C) #23I and D) #59 were applied to N2a/22L cells for 72 hours. Cells were then transferred to 96 well plates and allowed to attach overnight. The MTS colorimetric solution was added and allowed to incubate for 2–3 hours before reading absorbance at 490 nm. Graphs are plotted as percent cell survival compared to non-treated control. Only fluphenazine at 10 µM concentration was significantly toxic; ***<i>p</i><0.0001, Student's <i>t</i>-test, two-tailed.</p>", "links"=>[], "tags"=>["geriatrics", "molecular biology", "microbiology", "neuroscience", "pharmacology", "pathology", "neurological disorders", "Non-clinical medicine", "Infectious diseases"], "article_id"=>406397, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytotoxicity_Assay_/406397", "title"=>"Cytotoxicity Assay.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:46:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/373131"], "description"=>"<div><p>Prion diseases currently have no effective therapy. These illnesses affect both animal and human populations, and are characterized by the conformational change of a normal self protein PrP<sup>C</sup> (C for cellular) to a pathological and infectious conformer, PrP<sup>Sc</sup> (Sc for scrapie). We used a well characterized tissue culture model of prion infection, where mouse neuroblastoma cells (N2a) were infected with 22L PrP<sup>Sc</sup>, to screen compounds for anti-prion activity. In a prior study we designed a library of styryl based, potential imaging compounds which were selected for high affinity binding to Alzheimer's disease β-amyloid plaques and good blood-brain barrier permeability. In the current study we screened this library for activity in the N2a/22L tissue culture system. We also tested the anti-prion activity of two clinically used drugs, trimipramine and fluphenazine, in the N2a/22L system. These were selected based on their structural similarity to quinacrine, which was previously reported to have anti-prion activity. All the compounds were also screened for toxicity in tissue culture and their ability to disaggregate amyloid fibrils composed of PrP and β-amyloid synthetic peptides in vitro. Two of the imaging agents, 23I and 59, were found to be both effective at inhibiting prion infection in N2a/22L tissue culture and to be non-toxic. These two compounds, as well as trimipramine and fluphenazine were evaluated in vivo using wild-type CD-1 mice infected peripherally with 139A PrP<sup>Sc</sup>. All four agents significantly prolonged the asymptomatic incubation period of prion infection (p<0.0001 log-rank test), as well as significantly reducing the degree of spongiform change, astrocytosis and PrP<sup>Sc</sup> levels in the brains of treated mice. These four compounds can be considered, with further development, as candidates for prion therapy.</p> </div>", "links"=>[], "tags"=>["styryl-based", "tricyclic", "compounds", "anti-prion", "agents"], "article_id"=>133687, "categories"=>["Cancer", "Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Styryl_Based_and_Tricyclic_Compounds_as_Potential_Anti_Prion_Agents/133687", "title"=>"Styryl-Based and Tricyclic Compounds as Potential Anti-Prion Agents", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-09-13 01:01:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/737110"], "description"=>"<p>Thioflavin T fluorescence of compounds incubated with A) PrP 106-126 and B) Aβ42 fibrils for 72 hours. Compounds incubated with both with PrP 106-126 and Aβ42 significantly lowered fluorescence intensity. <i>p</i><0.0001 by One-way ANOVA; *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 Newman-Keuls <i>post-hoc</i> analysis of compounds versus peptide control.</p>", "links"=>[], "tags"=>["pre-formed", "prp106-126", "42"], "article_id"=>407458, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g011", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Disaggregation_of_Pre_formed_PrP106_126_and_A_946_42_Fibrils_/407458", "title"=>"Disaggregation of Pre-formed PrP106-126 and Aβ 42 Fibrils.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 02:04:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/736310"], "description"=>"<p>Graphs were plotted as percent inhibition of PrP<sup>Sc</sup> infectivity versus log of dose. IC<sub>50</sub> values are 0.7296 µM for fluphenazine, 1.289 µM for trimipramine, 18.01 µM for #23I and 17.03 µM for #59.</p>", "links"=>[], "tags"=>["concentrations", "trimipramine", "59", "half-maximal", "inhibitory", "fluphenazine"], "article_id"=>406653, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibitory_Concentrations_IC_50_for_Fluphenazine_23I_Trimipramine_and_59_Half_maximal_inhibitory_concentrations_IC_50_for_A_fluphenazine_B_23I_C_trimipramine_and_D_59_/406653", "title"=>"Inhibitory Concentrations (IC<sub>50</sub>) for Fluphenazine, 23I, Trimipramine and 59 Half-maximal inhibitory concentrations (IC<sub>50</sub>) for A) fluphenazine B) #23I C) trimipramine and D) #59.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:50:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/736870"], "description"=>"<p>Histological sections immunostained with anti-GFAP polyclonal antibody were quantified using Bioquant NovaPrime image analysis. A,B) Histological representation of non-treated control animal at 25× and 100× magnification, respectively (scale bars corresponding to 100 and 400 µm are shown). C,D) Shows representative sections from a treatment group (#23I) at 25× and 100× magnification. E) Shows a bar graph of the immunoreactivity quantitation for all groups. Graphs were plotted as percent immunoreactivity per area. Differences were significant by One-way ANOVA; <i>p</i> = 0.0073.</p>", "links"=>[], "tags"=>["immunoreactivity"], "article_id"=>407225, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g010", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GFAP_Immunoreactivity_as_a_Measure_of_Astrocytosis_/407225", "title"=>"GFAP Immunoreactivity as a Measure of Astrocytosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 02:00:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/736578"], "description"=>"<p>Brain homogenates of clinically symptomatic animals were PK-digested to assess PrP<sup>Sc</sup> levels. A) Shows a Western blot of a representative single mouse from each treatment group. B) Bar graph representation of total group brain homogenate PrP<sup>Sc</sup> levels as measured by O.D. of Western blots. The vehicle group is set as 100%. The mean values as a percentage of the vehicle control group are 68%, 83%, 80% and 85% for the fluphenazine, trimipramine, 23I and 59 groups, respectively. (<i>p</i><0.05 by one-way ANOVA). Compared to vehicle control <i>p</i> = 0.01 for fluphenazine, <i>p</i> = 0.02 for trimipramine, <i>p</i> = .002 for 23I and <i>p</i> = 0.02 for 59 (by two-tailed t test).</p>", "links"=>[], "tags"=>["geriatrics", "molecular biology", "microbiology", "neuroscience", "pharmacology", "pathology", "neurological disorders", "Non-clinical medicine", "Infectious diseases"], "article_id"=>406922, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g008", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Level_of_PrP_Sc_in_the_Brain_/406922", "title"=>"Level of PrP<sup>Sc</sup> in the Brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:55:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/736401"], "description"=>"<p>Survival analysis. The Kaplan-Meier survival curve shows significant treatment effects for all treatment groups. Survival analysis by log-rank test gave <i>p</i> values of: <i>p</i> = 0.0005 for fluphenazine, <i>p</i> = 0.0001 for trimipramine, <i>p</i><0.0001 for #23I, and <i>p</i><0.0001 for #59. The median survival for treatment groups were 205 dpi for fluphenazine, 210 dpi for trimipramine, 202 dpi for #23I, 215 dpi for #59 compared to 170 dpi for control. One animal in the trimipramine group remained clinically asymptomatic at 400 dpi, when it was sacrificed.</p>", "links"=>[], "tags"=>["geriatrics", "molecular biology", "microbiology", "neuroscience", "pharmacology", "pathology", "neurological disorders", "Non-clinical medicine", "Infectious diseases"], "article_id"=>406743, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_Survival_Curve_/406743", "title"=>"Kaplan-Meier Survival Curve.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:52:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/735946"], "description"=>"<p>A,B) #23I and C,D) #59 were applied to N2a/22L for 72 hrs at 0.5, 1.0, 2.5, 5, 10, and 20 µM. A,C) Blots represent proteinase-K digested cell lysates detected with 6D11 anti-PrP monoclonal antibody. Bands respresent di-, mono-, and non-glycosylated isoforms at approximately 28, 23 and 17 kDa respectively. B,D) Bar graph representations of percent PrP<sup>Sc</sup> infectivity compared to non-treated control (N2a/22L). B) #23I reduced PrP<sup>Sc</sup> levels by 98.4%, 88.1%, 86.5%, 73.5%, 67.2% and 56.4%. D) #59 reduced PrP<sup>Sc</sup> levels by 96.8%, 92.4%, 85.4%, 79.5%, 73.9% and 54.0%. Differences are significant by One-way ANOVA (**<i>p</i> = 0.0011), and *<i>p</i><0.05 Newman-Keuls <i>post-hoc</i> analysis versus N2a/22L as indicated on the graph.</p>", "links"=>[], "tags"=>["styryl-based", "compounds", "23i", "59"], "article_id"=>406294, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_Prion_Activity_of_Styryl_based_Compounds_23I_and_59_Styryl_based_compounds_/406294", "title"=>"Anti-Prion Activity of Styryl-based Compounds 23I and 59 Styryl-based compounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:44:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/736141"], "description"=>"<p>Fluphenazine. A) Shows the structure of fluphenazine. Fluphenazine was applied to N2a/22L for 72 hrs at 0.1, 0.5, 1.0 and 2.5 µM. B) Western blot of PK-digested cell lysates. C) Bar graph representation of PrP<sup>Sc</sup> reduction. Fluphenazine reduces PrP<sup>Sc</sup> infectivity by 84.8%, 75.5%, 24.0% and 2.9% respectively. Differences are significant by One-way ANOVA (***<i>p</i><0.0001), and *<i>p</i><0.05 Newman-Keuls <i>post-hoc</i> analysis versus N2a/22L as indicated on the graph.</p>", "links"=>[], "tags"=>["anti-prion"], "article_id"=>406497, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structure_and_Anti_Prion_Activity_of_Fluphenazine_/406497", "title"=>"Structure and Anti-Prion Activity of Fluphenazine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:48:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/736220"], "description"=>"<p>Trimipramine. A) Shows the structure of trimipramine. Trimipramine was applied to N2a/22L for 72 hrs at 0.1, 0.5, 1.0, 2.5 and 5 µM. B) Western blot of PK-digested cell lysates. C) Bar graph representation of PrP<sup>Sc</sup> reduction. Trimipramine reduces PrP<sup>Sc</sup> infectivity by 89.6%, 77.7%, 68.2%, 22.7% and 5.6% respectively. Differences are significant by One-way ANOVA (***<i>p</i><0.0001), and *<i>p</i><0.05 Newman-Keuls <i>post-hoc</i> analysis versus N2a/22L as indicated on the graph.</p>", "links"=>[], "tags"=>["anti-prion"], "article_id"=>406578, "categories"=>["Cell Biology", "Medicine", "Neuroscience", "Microbiology", "Infectious Diseases", "Pharmacology", "Molecular Biology"], "users"=>["Erika Chung", "Frances Prelli", "Stephen Dealler", "Woo Sirl Lee", "Young-Tae Chang", "Thomas Wisniewski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0024844.g004", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structure_and_Anti_Prion_Activity_of_Trimipramine_/406578", "title"=>"Structure and Anti-Prion Activity of Trimipramine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-13 01:49:38"}

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