10.6084/m9.figshare.9505346.v1
Omid Khalili Arjomandi
Omid Khalili
Arjomandi
Mahboubeh Kavoosi
Mahboubeh
Kavoosi
Hadi Adibi
Hadi
Adibi
Synthesis and enzyme-based evaluation of analogues <i>L</i>-tyrosine thiol carboxylic acid inhibitor of metallo-β-lactamase IMP-1
Taylor & Francis Group
2019
β-lactam
β-antibiotic resistance
metallo-β-lactamase
inhibitor
computational modelling
2019-08-12 04:32:03
Dataset
https://tandf.figshare.com/articles/dataset/Synthesis_and_enzyme-based_evaluation_of_analogues_i_L_i_-tyrosine_thiol_carboxylic_acid_inhibitor_of_metallo-_-lactamase_IMP-1/9505346
<p>The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of β-lactam antibiotics. Infections caused by some bacteria which secrete metallo-β-lactamases (enzymes that inactivate β-lactam antibiotics) are increasingly prevalent and have become a major worldwide threat to human health. These bacteria are resistant to β-lactam antibiotics and MBL-inhibitor/β-lactam antibiotic combination therapy can be a strategy to overcome this problem. So far, no clinically available inhibitors of metallo-β-lactamases (MBLs) have been reported. In this study, <i>L</i>-benzyl tyrosine thiol carboxylic acid analogues (<b>2a–2k</b>) were synthesized after the study of computational simulation by adding of methyl, chloro, bromo and nitro groups to the benzyl ring for investigation of SAR analysis. Although the synthesized molecules <b>2a–k</b> shows the potent inhibitory effects against metallo-β-lactamase (IMP-1) with the range of <i>K<sub>ic</sub></i> values of 1.04<b>–</b>4.77 µM, they are not as potent as the candidate inhibitor.</p>