In one aspect, use of compounds as active agents to treat a hearing impairment and to prevent a hearing impairment, and methods of treating and/or preventing hearing impairments or disorders using the compositions are disclosed. (E)-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)-S,6-dihydropyridin-2(1H)-one and derivatives exhibit excellent protection against antibiotic-induced hearing loss in zebrafish and mice. In one aspect, (E)-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)-S,6-dihydropyridin-2(1H)-one and derivatives can be used as a therapy for the treatment and/or prevention of hearing loss. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.