- Selectively Guanidinylated Aminoglycosides as Antibiotics
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The emergence of virulent, drug-resistant bacterial strains coupled with a minimal output of new pharmaceutical agents to combat them makes this a critical time for antibacterial research. Aminoglycosides are a well-studied, highly potent class of naturally occurring antibiotics with scaffolds amenable to modification, and therefore, they provide an excellent starting point for the development of semisynthetic, next-generation compounds. To explore the potential of this approach, we synthesized a small library of aminoglycoside derivatives selectively and minimally modified at one or two positions with a guanidine group replacing the corresponding amine or hydroxy functionality. Most guanidino-aminoglycosides showed increased affinity for the ribosomal decoding rRNA site, the cognate biological target of the natural products, when compared with their parent antibiotics, as measured by an in vitro fluorescence resonance energy transfer (FRET) A-site binding assay. Additionally, certain analogues showed improved minimum inhibitory concentration (MIC) values against resistant bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA). An amikacin derivative holds particular promise with activity greater than or equal to the parent antibiotic in the majority of bacterial strains tested.
- Fair, Richard J.,Hensler, Mary E.,Thienphrapa, Wdee,Dam, Quang N.,Nizet, Victor,Tor, Yitzhak
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experimental part
p. 1237 - 1244
(2012/08/29)
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- INHALED FOSFOMYCIN/TOBRAMYCIN FOR THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
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The present invention provides the use of an aerosol formulation comprising fosfomycin and tobramycin in the treatment of patients with chronic obstructive pulmonary disease (COPD) who are experiencing or are at risk of experiencing acute exacerbations of COPD. Formulations for such use and methods of treating humans with COPD are also provided.
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- Site-specific aminoglycoside derivatives and their use in immunodiagnostic assays
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A method of making a derivatized aminoglycoside includes reacting an aminoglycoside with at least 2 equivalents of a divalent metal ion in an aprotic solvent to complex two neighboring amino group and hydroxyl group pairs; reacting the non-complexed amino groups with a protecting reagent to provide protecting groups; removing the divalent metal ion to provide two unprotected amino groups; reacting one of the unprotected amino groups with a reactive substance containing an linker, a carrier, or a label; and removing the protecting groups. This method can be used to produce novel compounds and reagents.
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- Trans and cis traumatic acid salts having cicatrizant activity associated to bacteriostatic, antiviral, antibiotic or antifungal activity
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Traumatic acid salts, wherein B is a cation selected from: a) a quaternary ammonium, b) a cation of a linear or branched C1 -C20 mono-, di- or trialkanolamine, c) a cation of a biologically active primary, secondary or tertiary amine, d) silver or zinc cation, and relative pharmaceutical compositions administrable by topical or parenteral route For the therapeutic treatment of cutaneous pathologies in which it is important to associate an a bacteriostatic, antibiotic, antifungal or an antiviral activity, to the cicatrizant effect, typical of traumatic acid.
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- Method for apparatus for a defined serumfree medical solution useful for corneal preservation
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A defined serumfree medical solution for applications in Ophthalmology, that contains one or more cell nutrient supplements which maintains and enhances the preservation of eye tissues, including human corneal tissues at low temperatures (2° C. to 15° C.). This solution is composed of a defined aqueous nutrient and electrolyte solution, supplemented with a glycosaminoglycan(s), a deturgescent agent(s), an energy source(s), a buffer system(s), an antioxidant(s), membrane stabilizing components, antibiotic(s), ATP precursors and nutrient cell supplements.
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- Epiminodeaminodeoxyaminoglycoside antibiotics and intermediates
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Deoxyaminoglycoside antibiotics are prepared in a high yield from phosphorylated aminoglycosides by reacting a phosphorylated aminoglycoside (a) with a silylating agent, or (b) successively with (i) a silylating or acylating agent and (ii) a halogenating agent; then subjecting thus obtained intermediate to reduction. Deoxyaminoglycoside antibiotics are useful for treating infections caused by microorganisms which are resistant or non-resistant to the corresponding aminoglycoside antibiotics.
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- Dehydroxylation of aminosugars
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Dehydroxylation of aminoglycoside antibiotics is carried out by halogenation of phosphorylated aminoglycoside antibiotics followed by reduction of thus halogenated antibiotics. The dehydroxylation process is entirely new and gives the final product in a high yield. The resulting deoxyaminoglycoside antibiotics are effective against microorganisms including aminoglycoside antiobiotics-resistant microorganisms.
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