Zha Liang, Xie Yunfeng, Wu Chengyao, Lei Ming, Lu Xueer, Tang Wenjian, Zhang Jing
School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China.
Eur J Med Chem. 2022 Jun 5;236:114333. doi: 10.1016/j.ejmech.2022.114333. Epub 2022 Mar 31.
Novel benzothiazole‒urea hybrids were designed, synthesized and evaluated their anti-bacterial activity. They only exhibited anti-bacterial activity against Gram-positive bacteria, including clinical methicillin-resistant S. aureus (MRSA), compounds 5f, 5i, 8e, 8k and 8l exhibited potent activity (MIC = 0.39 and 0.39/0.78 μM against SA and MRSA, respectively). Crystal violet assay showed that compounds 5f, 8e and 8l not only inhibited the formation of biofilms but also eradicated preformed biofilms. Compound 8l had membrane disruption, little propensity to induce resistance, benign safety and in vivo anti-MRSA efficacy in a mouse model of abdominal infection. Therefore, our data demonstrated the potential to advance benzothiazole‒urea hybrids as a new class of antibiotics.
设计、合成了新型苯并噻唑-脲杂化物，并对其抗菌活性进行了评估。它们仅对革兰氏阳性菌表现出抗菌活性，包括临床耐甲氧西林金黄色葡萄球菌（MRSA），化合物5f、5i、8e、8k和8l表现出强效活性（对金黄色葡萄球菌和MRSA的MIC分别为0.39和0.39/0.78 μM）。结晶紫试验表明，化合物5f、8e和8l不仅抑制生物膜的形成，还能根除预先形成的生物膜。化合物8l具有膜破坏作用，诱导耐药的倾向小，安全性良好，在腹部感染小鼠模型中具有体内抗MRSA疗效。因此，我们的数据证明了将苯并噻唑-脲杂化物作为一类新型抗生素进行开发的潜力。
