scholarly journals Discovery of 2-Aminothiazoles as Potent Antiprion Compounds

2009 ◽  
Vol 84 (7) ◽  
pp. 3408-3412 ◽  
Author(s):  
Sina Ghaemmaghami ◽  
Barnaby C. H. May ◽  
Adam R. Renslo ◽  
Stanley B. Prusiner
Keyword(s):  
Small Molecules ◽  
Prion Diseases ◽  
Neuroblastoma Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lead Compounds ◽  
Primary Screening ◽  
Structure Activity ◽  
Neuroblastoma Cell Lines ◽  
Efficacy Studies

ABSTRACT Prion diseases are fatal, untreatable neurodegenerative diseases caused by the accumulation of the misfolded, infectious isoform of the prion protein (PrP), termed PrPSc. In an effort to identify novel inhibitors of prion formation, we utilized a high-throughput enzyme-linked immunosorbent assay (ELISA) to evaluate PrPSc reduction in prion-infected neuroblastoma cell lines (ScN2a). We screened a library of ∼10,000 diverse small molecules in 96-well format and identified 121 compounds that reduced PrPSc levels at a concentration of 5 μM. Four chemical scaffolds were identified as potential candidates for chemical optimization based on the presence of preliminary structure-activity relationships (SAR) derived from the primary screening data. A follow-up analysis of a group of commercially available 2-aminothiazoles showed this class as generally active in ScN2a cells. Our results establish 2-aminothiazoles as promising candidates for efficacy studies of animals and validate our drug discovery platform as a viable strategy for the identification of novel lead compounds with antiprion properties.

The DNA-binding protein YB-1 is a direct MYCN target and influences repair and resistance in neuroblastoma cell lines

2010 ◽  
Vol 222 (03) ◽  
Author(s):  
S Degen ◽  
S Kuhfittig-Kulle ◽  
JH Schulte ◽  
F Westermann ◽  
A Schramm ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cell Lines ◽  
Binding Protein ◽  
Neuroblastoma Cell ◽  
Dna Binding Protein ◽  
Neuroblastoma Cell Lines

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Mechanism Of Action ◽  
Marine Natural Products ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Follow Up Studies ◽  
Initial Resistance ◽  
Synthesis And Biological Evaluation

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

Negative and positive effects of an IAP-LTR on nearby Pcdaα gene expression in the central nervous system and neuroblastoma cell lines

Gene ◽  
2004 ◽  
Vol 337 ◽  
pp. 91-103 ◽  
Author(s):  
Hidehiko Sugino ◽  
Tomoko Toyama ◽  
Yusuke Taguchi ◽  
Shigeyuki Esumi ◽  
Mitsuhiro Miyazaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Positive Effects ◽  
The Central Nervous System ◽  
Neuroblastoma Cell Lines

scholarly journals Anti-HPV16 Antibody Titers Prior to an Incident Cervical HPV16/31 Infection

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1548
Author(s):  
Ana Gradissimo ◽  
Viswanathan Shankar ◽  
Fanua Wiek ◽  
Lauren St. Peter ◽  
Yevgeniy Studentsov ◽  
...  
Keyword(s):  
High Risk ◽  
Hpv Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Incident Detection ◽  
Antibody Titers ◽  
Circulating Antibodies ◽  
Prospective Association ◽  
Nested Case Control ◽  
Incident Cases

The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine longitudinal cohort at Mount Sinai Adolescent Health Center in Manhattan, NY. We performed a nested case–control study of 43 cases with incident detection of cervical HPV16 (n = 26) or HPV31 (n = 17) DNA who had completed the full set of immunizations of the quadrivalent HPV vaccine (4vHPV). Two control individuals whom had received three doses of the vaccine (HPV16/31-negative) were selected per case, matched on age at the first dose of vaccination and follow-up time in the study: a random control, and a high-risk control that was in the upper quartile of a sexual risk behavior score. We conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G (IgG) antibodies specific to anti-HPV16 virus-like particles (VLPs). The results suggest that the average log antibody titers were higher among high-risk controls than the HPV16/31 incident cases and the randomly selected controls. We show a prospective association between anti-HPV16 VLP titers and the acquisition of an HPV16/31 incident infection post-receiving three doses of 4vHPV vaccine.

scholarly journals Plasticity in Neuroblastoma Cell Identity Defines a Noradrenergic-to-Mesenchymal Transition (NMT)

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2904
Author(s):  
Margot Gautier ◽  
Cécile Thirant ◽  
Olivier Delattre ◽  
Isabelle Janoueix-Lerosey
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Biochemical Properties ◽  
Poor Overall Survival ◽  
Cell Identity ◽  
Mesenchymal Transition ◽  
Neuroblastoma Cell Lines

Neuroblastoma, a pediatric cancer of the peripheral sympathetic nervous system, is characterized by an important clinical heterogeneity, and high-risk tumors are associated with a poor overall survival. Neuroblastoma cells may present with diverse morphological and biochemical properties in vitro, and seminal observations suggested that interconversion between two phenotypes called N-type and S-type may occur. In 2017, two main studies provided novel insights into these subtypes through the characterization of the transcriptomic and epigenetic landscapes of a panel of neuroblastoma cell lines. In this review, we focus on the available data that define neuroblastoma cell identity and propose to use the term noradrenergic (NOR) and mesenchymal (MES) to refer to these identities. We also address the question of transdifferentiation between both states and suggest that the plasticity between the NOR identity and the MES identity defines a noradrenergic-to-mesenchymal transition, reminiscent of but different from the well-established epithelial-to-mesenchymal transition.

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