Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents.
Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents.
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鉴定 5,6-二氢咪唑并[2,1-b]噻唑作为一类新型抗菌剂。
DOI：
10.1016/j.bmc.2016.09.027
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发表时间：
2016
影响因子：
3.5
通讯作者：
Shaw,Lindsey
中科院分区：
文献类型：
--
作者：
Li,Yangmei;Bionda,Nina;Fleeman,Renee;Wang,Hongjie;Ozawa,Akihiko;Houghten,RichardA;Shaw,Lindsey
为了开发针对耐药细菌感染的新型抗菌剂，合成了5，6-二氢咪唑并[2，1-b]噻唑类化合物，并对其进行了抗菌活性测试。由两个亚支架组成的八个化合物被鉴定为对耐甲氧西林金黄色葡萄球菌(MRSA)的抑制作用。通过将(S)-6取代为(R)-6构型，这些HITS在6位被修饰，(R)-异构体的抗菌活性增加了一倍。在标准微量稀释法中，最具活性的化合物对耐甲氧西林金黄色葡萄球菌的MIC90值为3.7g/μ。该化合物以5倍最低抑菌浓度(MIC)的剂量，通过线虫感染模型保护蜡蛾对MRSA的抗性。在DNA旋转酶超螺旋实验中，该化合物也表现出对DNA旋转酶活性的抑制，这表明5，6-二氢咪唑并[2，1-b]噻唑可能针对DNA旋转酶的抗菌作用。
In an effort to develop novel antimicrobial agents against drug-resistant bacterial infections, 5,6-dihydroimidazo[2,1-b]thiazole compounds were synthesized and tested for their antimicrobial activity. Eight compounds comprised by two sub-scaffolds were identified as hits against methicillin-resistantStaphylococcus aureus(MRSA). These hits were modified at 6-position by replacing (S)-6 to (R)-6 configuration and the (R)-isomers increased their antimicrobial activities by two-fold. The most active compound showed a MIC90value of 3.7 μg/mL against MRSA in a standard microdilution bacterial growth inhibitory assay. This compound protected wax moth worms against MRSA at a dose of 5× MIC using a worm infectious model. This compound also exhibited inhibition of DNA gyrase activity in a DNA gyrase supercoil assay, suggesting the 5,6-dihydroimidazo[2,1-b]thiazoles may target DNA gyrase for the antimicrobial action.