title: Biological evaluation of halogenated thiazolo[3,2-a]pyrimidin-3-one carboxylic acid derivatives targeting the YycG histidine kinase.
abstract: With an intention to potent inhibitors of YycG histidine kinase, a series of halogenated thiazolo[3,2-a]pyrimidin-3-one carboxylic acid derivatives were synthesized and evaluated for their antibacterial, antibiofilm and hemolytic activities. The majority of the compounds showed good activity against Staphylococcus epidermidis and Staphylococcus aureus, with MIC values of 1.56-6.25 μM, simultaneously presented promising antiobifilm activity against S. epidermidis ATCC35984 at 50 μM. The test of inhibitory activity on YycG kinase suggested the antibacterial activities of these derivatives are based on inhibiting the enzyme activity of the YycG HK domain. The hemolytic activity test suggested these compounds exhibited in vitro antibacterial activity at non-hemolytic concentrations.
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211816, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211816, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministry of Education and Ministry of Public Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical School of Fudan University Box 228, Shanghai 200032, China.
authors.forename: Huayong
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211816, China.
authors.forename: Likang
authors.initials: L
authors.lastname: Zheng
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211816, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministry of Education and Ministry of Public Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical School of Fudan University Box 228, Shanghai 200032, China. Electronic address: dqu@shmu.edu.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211816, China. Electronic address: hanshiqing@njut.edu.cn.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Han
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms; D002264:Carboxylic Acids / Q000737:chemistry*; D006219:Halogens / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D000071677:Histidine Kinase; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011494:Protein Kinases / Q000187:drug effects*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D006219:Halogens; D011743:Pyrimidines; D013844:Thiazoles; D011494:Protein Kinases; D000071677:Histidine Kinase; C515949:YycG protein, Staphylococcus epidermidis
keywords: Antibacterial activity; Antibiofilm activity; Halogenated thiazolo[3,2-a]pyrimidin-3-one; Staphylococcus aureus; Staphylococcus epidermidis; YycG histidine kinase inhibitor