Cui Penglei, Li Xiaoliu, Zhu Mengyuan, Wang Binghe, Liu Jing, Chen Hua
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China; College of Science, Agricultural University of Hebei, Baoding 071001, China.
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
Bioorg Med Chem Lett. 2017 May 15;27(10):2234-2237. doi: 10.1016/j.bmcl.2016.11.060. Epub 2016 Nov 23.
A series of novel thiouracil derivatives containing an acyl thiourea moiety (7a-7x) have been synthesized by structural modification of a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7c, 7m, 7u, 7v exhibited promising activities against above bacteria. Such four compounds were further tested for their inhibitory activity against SecA ATPase, and the results showed that compounds 7c and 7u had higher inhibitory activities than that of compound 2. Molecular docking work suggests that compound 7u might bind at a pocket close to the ATPase ATP-binding domain.
通过对先导SecA抑制剂2进行结构修饰，合成了一系列含有酰基硫脲部分的新型硫脲衍生物（7a - 7x）。所有化合物均针对解淀粉芽孢杆菌、金黄色葡萄球菌和枯草芽孢杆菌进行了抗菌活性评估。化合物7c、7m、7u、7v对上述细菌表现出有前景的活性。对这四种化合物进一步测试了它们对SecA ATP酶的抑制活性，结果表明化合物7c和7u的抑制活性高于化合物2。分子对接研究表明化合物7u可能结合在靠近ATP酶ATP结合结构域的一个口袋处。
