Carbohydr Res
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
Published: May 2013
Ménière's disease (MD) is a progressive disease of the inner ear characterized by recurring attacks of disabling vertigo, hearing loss and tinnitus. Patients who do not respond to vestibular sedatives or steroids may require an intratympanic application of aminoglycoside antibiotics, which destroys the vestibular function of the affected ear in order to avoid the debilitating vertigo attacks. Although effective, this procedure causes hearing loss in almost one third of the patients due to the aminoglycosides cochlear toxicity. Here we describe the synthesis of two pseudodisaccharides structurally related to neamime aiming to mimic the aminoglycosides pharmacophore core by replacing their toxic amine by azide and hydroxyl groups. Products 1 and 2 selectively promoted 'in vivo' damage to vestibular tissues without causing hearing loss or cochlear toxicity. Therefore, these pseudodisaccharides stand as promising lead compounds for the development of a safer and more effective therapeutic procedure to manage the symptoms of MD severe dizziness.
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http://dx.doi.org/10.1016/j.carres.2013.03.019 | DOI Listing |
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