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Development of Tetrazole Based inhibitor against multple classes of Carbapenemases
EP27230
Poster Title: Development of Tetrazole Based inhibitor against multple classes of Carbapenemases
Submitted on 22 Feb 2018
Author(s): Afroza Akhtar
Affiliations: Morsani College of Medicine, University of South Florida
This poster was presented at USF Health Research Day 2018
Poster Views: 483
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Poster Information
Abstract: Carbapenemases are the most versatile family of β-lactamases which are capable of hydrolyzing virtually all β-lactam antibiotics including carbapenem, the last resort of treatment in the clinical settings to treat bacterial infection. Previous studies have showed that tetrazole compounds can act as a potent inhibitor against extended spectrum β-lactamase CTX-M. Here we found a tetrazole compound in the active site of KPC-2 (class A carbapenemase), NDM-1(class B carbapenemase) and OXA-48(class D carbapenemase). For all those enzymes, the compound exhibit activity in microM level. This study provides both biochemical and biophysical report to show that tetrazole based inhibitors could be used as a potential scaffold to target different classes of carbapenemases in a non-covalent fashion.
Summary: This project centers on developing non-covalent β-lactamase inhibitors, which may represent a possible effort in countering bacterial resistance due to carbapenemases.
References:
Chen et al Molecular docking and ligand specificity in fragment-based inhibitor discovery; Nat. Chem. Biol. 5: 358-364 (2009):
Derek A. Nicholset.al; Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A β-Lactamase; J. Med. Chem., 2012, 55 (5), pp 2163–2172; DOI: 10.1021/jm2014138
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