{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Durcik M"],"funding":["National Academy of Sciences","Innovative Medicines Initiative","H2020 European Institute of Innovation and Technology","Javna Agencija za Raziskovalno Dejavnost RS","DBT/Wellcome Trust India Alliance","Redx Pharma Plc","Nemzeti Kutatási Fejlesztési és Innovációs Hivatal","European Federation of Pharmaceutical Industries and Associations","European Research Council","National Laboratory of Biotechnology","Seventh Framework Programme","ELKH Lendület Programme","Wellcome Trust","Biotechnology and Biological Sciences Research Council"],"pagination":["3968-3994"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10041525"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["66(6)"],"pubmed_abstract":["A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive <i>Enterococcus faecalis</i>, <i>Enterococcus faecium</i> and multidrug resistant (MDR) <i>Staphylococcus aureus</i> strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125-0.25 μg/mL] and against the Gram-negatives <i>Acinetobacter baumannii</i> and <i>Klebsiella pneumoniae</i> (best compound MICs: range, 1-4 μg/mL). Lead compound <b>7a</b> was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of <b>7a</b> in complex wi"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate <i>Staphylococcus aureus</i>."],"pmcid":["PMC10041525"],"funding_grant_id":["FP7/2007-2013","110072/Z/15/Z","BI-HU/19-20-008","NKFIH-871-3/2020","LP-201710/2020","2022-2.1.1-NL-2022-00008","648364","BB/J014524/1","BBS/E/J/000CA547","115583","P1-0208","BB/P012523/1","KKP 126506","BBS/E/J/000PR9791","J1-3030","J1-3031"],"pubmed_authors":["Trontelj J","Sterk GJ","Durcik M","Maharramov E","Kikelj D","Alver S","Mundy JEA","Czikkely M","Pal C","Toplak Z","Vicente F","Berruga-Fernandez T","Zega A","Maxwell A","Zidar N","Hughes D","Janssen GV","Tomasic T","Piras MV","Pardo LA","Stevenson CEM","Vu TH","Peterlin Masic L","Jin Z","Lawson DM","Ilas J","Mozina S","Huseby D","Skok Z","Glinghammar B","Cao S","Svensson R","Cotman AE","Korol SV","Ramos MC","Simoff I","Sjostrom E","Oreskar J","Szili PE","Bohlin M"],"additional_accession":[]},"is_claimable":false,"name":"New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate <i>Staphylococcus aureus</i>.","description":"A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive <i>Enterococcus faecalis</i>, <i>Enterococcus faecium</i> and multidrug resistant (MDR) <i>Staphylococcus aureus</i> strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125-0.25 μg/mL] and against the Gram-negatives <i>Acinetobacter baumannii</i> and <i>Klebsiella pneumoniae</i> (best compound MICs: range, 1-4 μg/mL). Lead compound <b>7a</b> was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of <b>7a</b> in complex wi","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2026-05-28T22:40:17.661Z","creation":"2024-11-06T04:39:00.732Z"},"accession":"S-EPMC10041525","cross_references":{"pubmed":["36877255"],"doi":["10.1021/acs.jmedchem.2c01905"]}}