Toward Overcoming Staphylococcus aureus Aminoglycoside Resistance Mechanisms with a Functionally Designed Neomycin Analogue.

Autor: Hanessian S; Department of Chemistry, Université de Montréal , C.P. 6128, Succ. Centre-Ville, Montréal, Quebec H3C 3J7, Canada., Giguère A; Department of Chemistry, Université de Montréal , C.P. 6128, Succ. Centre-Ville, Montréal, Quebec H3C 3J7, Canada., Grzyb J; Department of Chemistry, Université de Montréal , C.P. 6128, Succ. Centre-Ville, Montréal, Quebec H3C 3J7, Canada., Maianti JP; Department of Chemistry, Université de Montréal , C.P. 6128, Succ. Centre-Ville, Montréal, Quebec H3C 3J7, Canada., Saavedra OM; Department of Chemistry, Université de Montréal , C.P. 6128, Succ. Centre-Ville, Montréal, Quebec H3C 3J7, Canada., Aggen JB; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Linsell MS; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Goldblum AA; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Hildebrandt DJ; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Kane TR; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Dozzo P; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Gliedt MJ; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Matias RD; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Feeney LA; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States., Armstrong ES; Achaogen Inc. , 7000 Shoreline Court, Suite 371, South San Francisco, California 94080, United States.
Jazyk: angličtina
Zdroj: ACS medicinal chemistry letters [ACS Med Chem Lett] 2011 Sep 29; Vol. 2 (12), pp. 924-8. Date of Electronic Publication: 2011 Sep 29 (Print Publication: 2011).
DOI: 10.1021/ml200202y
Abstrakt: Deoxygenation of the diol groups in rings A and D of neomycin in combination with the introduction of an N1-(l)-HABA group in the 2-deoxystreptamine subunit (ring B) leads to a novel and potent antibiotic (1) with activity against strains of S. aureus carrying known aminoglycoside resistance determinants, as well as against an extended panel of Methicillin-resistant S. aureus isolates (n = 50). Antibiotic 1 displayed >64 fold improvement in MIC50 and MIC90 against this MRSA collection when compared to the clinically relevant aminoglycosides amikacin and gentamicin. The synthesis was achieved in six steps and 15% overall yield.
Databáze: MEDLINE
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