Quinoline Ring Derivatives Protect Against Aminoglycoside-Induced Hair Cell Death in the Zebrafish Lateral Line View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-10-10

AUTHORS

Henry C. Ou, Sarah Keating, Patricia Wu, Julian A. Simon, David W. Raible, Edwin W Rubel

ABSTRACT

We have previously published results from a screen of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection) for drugs that protect against neomycin-induced hair cell death (Ou et al., J Assoc Res Otolaryngol 10:191–203, 2009). Further evaluation of this drug library identified eight protective drugs that shared a common quinoline scaffold. These drugs were tested further in terms of their protection against other aminoglycosides, as well as their effect on aminoglycoside uptake. All of the eight quinolines that protected against neomycin were found to protect against short- and long-term gentamicin damage protocols. We then tested the structurally related compounds quinoline, isoquinoline, naphthalene, and indole for protective effects. Of these compounds, indole demonstrated a small but significant amount of protection against neomycin, while quinoline and isoquinoline partially protected against long-term gentamicin damage. We examined whether the protective activity of this group of compounds was related to known targets of the quinoline derivatives. The protective effects did not seem linked to either the cholinergic or histaminergic pathways that are regulated by some members of the quinoline family. However, all eight protective drugs were found to reduce the uptake of aminoglycosides into hair cells. Subsequent experiments suggest that reduction of uptake is the primary mechanism of protection among the quinoline drugs. More... »

PAGES

759-770

References to SciGraph publications

  • 2003-11-12. Uptake of Gentamicin by Bullfrog Saccular Hair Cells in vitro in JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
  • 2009-02-25. Identification of FDA-Approved Drugs and Bioactives that Protect Hair Cells in the Zebrafish (Danio rerio) Lateral Line and Mouse (Mus musculus) Utricle in JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10162-012-0353-0

    DOI

    http://dx.doi.org/10.1007/s10162-012-0353-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1043406624

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23053627


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