Zhao Dan, Chen Chen, Liu Huayong, Zheng Likang, Tong Yao, Qu Di, Han Shiqing
College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211816, China.
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.
Eur J Med Chem. 2014 Nov 24;87:500-7. doi: 10.1016/j.ejmech.2014.09.096. Epub 2014 Oct 2.
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.
为了寻找YycG组氨酸激酶的有效抑制剂，合成了一系列卤代噻唑并[3,2-a]嘧啶-3-酮羧酸衍生物，并对其抗菌、抗生物膜和溶血活性进行了评估。大多数化合物对表皮葡萄球菌和金黄色葡萄球菌表现出良好的活性，MIC值为1.56-6.25μM，同时在50μM时对表皮葡萄球菌ATCC35984具有良好的抗生物膜活性。对YycG激酶的抑制活性测试表明，这些衍生物的抗菌活性基于抑制YycG HK结构域的酶活性。溶血活性测试表明，这些化合物在非溶血浓度下表现出体外抗菌活性。
