title: New insights into the bacterial RNA polymerase inhibitor CBR703 as a starting point for optimization as an anti-infective agent.
abstract: CBR703 was reported to inhibit bacterial RNA polymerase (RNAP) and biofilm formation, considering it to be a good candidate for further optimization. While synthesized derivatives of CBR703 did not result in more-active RNAP inhibitors, we observed promising antibacterial activities. These again correlated with a significant cytotoxicity toward mammalian cells. Furthermore, we suspect the promising effects on biofilm formation to be artifacts. Consequently, this class of compounds can be considered unattractive as antibacterial agents.
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Design and Optimization, Saarland University, Saarbrücken, Germany.
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Design and Optimization, Saarland University, Saarbrücken, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Haupenthal
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Design and Optimization, Saarland University, Saarbrücken, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Groh
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Michelle
authors.initials: M
authors.lastname: Fountain
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Design and Optimization, Saarland University, Saarbrücken, Germany Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Germany rolf.hartmann@helmholtz-hzi.de.
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D000578:Amidines / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D012329:RNA, Bacterial / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000578:Amidines; D000900:Anti-Bacterial Agents; C478598:CBR 703; D004791:Enzyme Inhibitors; D006898:Hydroxylamines; D012329:RNA, Bacterial; D012321:DNA-Directed RNA Polymerases