Aminoglycoside antibiotic derivatives: preparation and evaluation of toxicity on cochlea and vestibular tissues and antimicrobial activity.
Aminoglycoside antibiotic derivatives such as neamine, methyl neobiosaminide B, 2-deoxystreptamine, tetra-azidoneamine, tetra-N-acetylneamine, tetra-N-carboxy-benzylneamine, tetra-N-carboxy-methylneamine and tetra-p-methoxy-benzyliminoneamine were prepared and evaluated as to their cochlear and vestibular toxicity. Methyl neobiosaminide B, the most promising derivative in the series showed selective, cochlea-dissociated vestibulotoxic activity and was considered to be a potential lead compound for the treatment of Ménière's disease. Antimicrobial properties of the compounds, qualitatively evaluated against a group of pathogenic bacteria, indicated that neomycin B sulfate, neamine as a free base and methyl-neobiosaminide B dihydrochloride show a broader range of activity when compared to the other derivatives.
da Silva
Julierme G
JG
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto-SP, Brazil.
Hyppolito
Miguel A
MA
de Oliveira
José Antônio A
JA
Corrado
Alexandre P
AP
Ito
Izabel Y
IY
Carvalho
Ivone
I
D000617:Aminoglycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D001419:Bacteria / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000648:ultrastructure; D006168:Guinea Pigs; D008855:Microscopy, Electron, Scanning; D013329:Structure-Activity Relationship; D014722:Vestibule, Labyrinth / Q000187:drug effects*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents