Zhang Jing, Huang Hao, Zhou Xueting, Xu Yingying, Chen Baochun, Tang Wenjian, Xu Kehan
Prevention and Treatment Center for Occupational Disease, Anhui No. 2 Provincial People's Hospital, Hefei 230022, China.
College of Basic Medical, Anhui Medical University, Hefei 230032, China.
ACS Med Chem Lett. 2019 Feb 28;10(3):329-333. doi: 10.1021/acsmedchemlett.8b00612. eCollection 2019 Mar 14.
Bacterial fatty acid synthase system is a well validated target for the development of novel antimicrobial agents. This study reports the synthesis of Schiff bases and their reductive -benzylanilines. Most -benzylanilines were active against Gram-positive bacteria, among which compound performed best against both and MRSA with the MIC value at 0.5 mg/L. Moreover, we identified the strong antibacterial activity for compound against 19 clinical MRSA strains isolated from different specimen, which indicated its potential in clinical application. biofilm inhibition and microscopy assay revealed compound inhibits biofilm formation and eradicates preformed biofilm effectively. The size-exclusion chromatography and docking study indicated that compound mimics the binding mode of triclosan with saFabI. The efficiency of the protein-inhibitor interaction was evaluated by measuring NADPH reduction using -2-octenoyl-CoA as substrate. Overall, our data demonstrate that -benzylaniline is a promising scaffold for anti-staphylococcal drug development.
细菌脂肪酸合酶系统是开发新型抗菌剂的一个经过充分验证的靶点。本研究报道了席夫碱及其还原苄基苯胺的合成。大多数苄基苯胺对革兰氏阳性菌有活性，其中化合物对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌（MRSA）表现最佳，MIC值为0.5 mg/L。此外，我们确定了化合物对从不同标本中分离出的19株临床MRSA菌株具有很强的抗菌活性，这表明其在临床应用中的潜力。生物膜抑制和显微镜分析表明，化合物可有效抑制生物膜形成并根除预先形成的生物膜。尺寸排阻色谱和对接研究表明，化合物模拟了三氯生与saFabI的结合模式。通过以-2-辛烯酰辅酶A为底物测量NADPH还原，评估了蛋白质-抑制剂相互作用的效率。总体而言，我们的数据表明，苄基苯胺是抗葡萄球菌药物开发的一个有前景的骨架。
