title: Efficacy of novel antibacterial compounds targeting histidine kinase YycG protein.
abstract: Treating staphylococcal biofilm-associated infections is challenging. Based on the findings that compound 2 targeting the HK domain of Staphylococcus epidermidis YycG has bactericidal and antibiofilm activities against staphylococci, six newly synthesized derivatives were evaluated for their antibacterial activities. The six derivatives of compound 2 inhibited autophosphorylation of recombinant YycG' and the IC50 values ranged from 24.2 to 71.2 μM. The derivatives displayed bactericidal activity against planktonic S. epidermidis or Staphylococcus aureus strains in the MIC range of 1.5-3.1 μM. All the derivatives had antibiofilm activities against the 6- and 24-h biofilms of S. epidermidis. Compared to the prototype compound 2, they had less cytotoxicity for Vero cells and less hemolytic activity for human erythrocytes. The derivatives showed antibacterial activities against clinical methicillin-resistant staphylococcal isolates. The structural modification of YycG inhibitors will assist the discovery of novel agents to eliminate biofilm infections and multidrug-resistant staphylococcal infections.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Science and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China.
authors.forename: Huayong
authors.initials: H
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Liang
authors.initials: L
authors.lastname: Yan
authors.forename: Fuju
authors.initials: F
authors.lastname: Zhao
authors.forename: Youcong
authors.initials: Y
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Ting
authors.initials: T
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Nianan
authors.initials: N
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Shiqing
authors.initials: S
authors.lastname: Han
authors.forename: Di
authors.initials: D
authors.lastname: Qu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D018441:Biofilms / Q000187:drug effects; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011494:Protein Kinases; C515949:YycG protein, Staphylococcus epidermidis
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