Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2015
Title: Membrane Disruption and Enhanced Inhibition of Cell-Wall Biosynthesis: A Synergistic Approach to Tackle Vancomycin-Resistant Bacteria
Authors: Yarlagadda, Venkateswarlu
Samaddar, Sandip
Paramanandham, Krishnamoorthy
Shome, Bibek R.
Haldar, Jayanta
Keywords: Chemistry
antibiotics
bacterial resistance
drugs design
multidrug-resistant bacteria
vancomycin
ALA-D-ALA
Glycopeptide Antibiotics Back
D-Lac Binding
Antibacterial Activity
Staphylococcus-Aureus
Discovery
Lipoglycopeptide
Oritavancin
Pathogens
Design
Issue Date: 2015
Publisher: Wiley-V C H Verlag Gmbh
Citation: Angewandte Chemie-International Edition
54
46
Yarlagadda, V.; Samaddar, S.; Paramanandham, K.; Shome, B. R.; Haldar, J., Membrane Disruption and Enhanced Inhibition of Cell-Wall Biosynthesis: A Synergistic Approach to Tackle Vancomycin-Resistant Bacteria. Angewandte Chemie-International Edition 2015, 54 (46), 13644-13649.
Abstract: Resistance to glycopeptide antibiotics, the drugs of choice for life-threatening bacterial infections, is on the rise. In order to counter the threat of glycopeptide-resistant bacteria, we report development of a new class of semi-synthetic glycopeptide antibiotics, which not only target the bacterial membrane but also display enhanced inhibition of cell-wall biosynthesis through increased binding affinity to their target peptides. The combined effect of these two mechanisms resulted in improved invitro activity of two to three orders of magnitude over vancomycin and no propensity to trigger drug resistance in bacteria. In murine model of kidney infection, the optimized compound was able to bring bacterial burden down by about 6 logs at 12mgkg(-1) with no observed toxicity. The results furnished in this report emphasize the potential of this class of compounds as future antibiotics for drug-resistant Gram-positive infections.
Description: Restricted access
URI: http://hdl.handle.net/10572/2015
ISSN: 1433-7851
Appears in Collections:Research Papers (Jayanta Haldar)

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