Exploring the Beneficial Effects of Quinoline Derivatives after Noise-Induced Damage
Abstract
More than 300 million people worldwide suffer from noise-induced hearing loss (NIHL), with members of the military service being a particular susceptible group due to their, sometimes unpredictable, exposure to intense acoustic trauma. Despite the enormous social and economic impact of NIHL there are currently no therapies to prevent or alleviate this condition. Published work and preliminary studies from our laboratory suggest that quinoline derivatives have the potential to protect against drug- and noise-induced hearing loss. The advantage of working with quinoline derivatives is that they have an excellent malleable structure for medicinal chemistry modifications, most of them are water soluble and stable at room temperature. Moreover, quinoline derivatives have been approved by the FDA for their use in the pharmaceutical and food industries, which could expedite their development as therapeutic compounds to treat hearing loss. The goal of this award is to synthesize, screen and identify quinoline derivatives that will protect against NIHL. During the first year of this proposal we synthesized 70 analogs that were then,tested in a zebrafish model for hair cell excitotoxicity. Out of the 70, 31 protected the hair cells from the kainic acid toxic effect. Of those 31, we have currently tested 7 for protection of the hair cell ribbon synapses. We found that only two, Qx-1 and Qx-62, prevented the loss of ribbon synapses. We are currently testing the rest of the 31 compounds to assess whether they can also prevent from kainic-acid induced synaptopathy. These results are significant not only because we were able to identify two compounds that have the potential to protect hair cells and synapses from excitotoxic damage but also because we will be able to move forward with, at least, those two compounds and test them in a mouse model for NIHL.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1196923
Entities
People
- Marisa Zallocchi
Organizations
- Creighton University