7 research outputs found
6â˛â˛âThioether Tobramycin Analogues: Towards Selective Targeting of Bacterial Membranes
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91322/1/ange_201200761_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91322/2/5750_ftp.pd
Site-Selective Displacement of Tobramycin Hydroxyls for Preparation of Antimicrobial Cationic Amphiphiles
A short site-selective strategy for the activation and derivatization of alcohols of the clinically important aminoglycoside tobramycin is reported. The choice of amine protecting group affected the site-selective conversion of secondary alcohols of tobramycin into leaving groups. Temperature-dependent, chemoselective sequential nucleophilic displacements resulted in hetero- and homodithioether tobramycin-based cationic amphiphiles that demonstrated marked antimicrobial activity and impressive membrane selectivity
Synthesis and Evaluation of Hetero- and Homodimers of Ribosome-Targeting Antibiotics: Antimicrobial Activity, in Vitro Inhibition of Translation, and Drug Resistance
In
this study, we describe the synthesis of a full set of homo-
and heterodimers of three intact structures of different ribosome-targeting
antibiotics: tobramycin, clindamycin, and chloramphenicol. Several
aspects of the biological activity of the dimeric structures were
evaluated including antimicrobial activity, inhibition of in vitro
bacterial protein translation, and the effect of dimerization on the
action of several bacterial resistance mechanisms that deactivate
tobramycin and chloramphenicol. This study demonstrates that covalently
linking two identical or different ribosome-targeting antibiotics
may lead to (i) a broader spectrum of antimicrobial activity, (ii)
improved inhibition of bacterial translation properties compared to
that of the parent antibiotics, and (iii) reduction in the efficacy
of some drug-modifying enzymes that confer high levels of resistance
to the parent antibiotics from which the dimers were derived
Inside Cover: 6â˛â˛âThioether Tobramycin Analogues: Towards Selective Targeting of Bacterial Membranes (Angew. Chem. Int. Ed. 23/2012)
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92017/1/5508_ftp.pd
Innentitelbild: 6â˛â˛âThioether Tobramycin Analogues: Towards Selective Targeting of Bacterial Membranes (Angew. Chem. 23/2012)
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91346/1/5602_ftp.pd