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Design, Synthesis, and Evaluation of Novel Tyrosine‐Based DNA Gyrase B Inhibitors
Author(s) -
Cotman Andrej E.,
Trampuž Marko,
Brvar Matjaž,
Kikelj Danijel,
Ilaš Janez,
PeterlinMašič Lucija,
Montalvão Sofia,
Tammela Päivi,
Frlan Rok
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700087
Subject(s) - dna gyrase , enterococcus faecalis , topoisomerase iv , chemistry , escherichia coli , staphylococcus aureus , topoisomerase , dna , antibacterial activity , protein subunit , minimum inhibitory concentration , microbiology and biotechnology , biochemistry , biology , in vitro , bacteria , gene , genetics
The discovery and synthesis of new tyrosine‐based inhibitors of DNA gyrase B (GyrB), which target its ATPase subunit, is reported. Twenty‐four compounds were synthesized and evaluated for activity against DNA gyrase and DNA topoisomerase IV. The antibacterial properties of selected GyrB inhibitors were demonstrated by their activity against Staphylococcus aureus and Enterococcus faecalis in the low micromolar range. The most promising compounds, 8a and 13e , inhibited Escherichia coli and S. aureus GyrB with IC 50 values of 40 and 30 µM. The same compound also inhibited the growth of S. aureus and E. faecalis with minimal inhibitory concentrations (MIC 90 ) of 14 and 28 µg/mL, respectively.