Wang Chun-Hua, Xie Xian-Rui, Liu Wen-Shuai, Hou Gui-Ge, Sun Ju-Feng, Zhao Feng, Cong Wei, Li Hong-Juan, Xin Wen-Yu
School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, China.
Chem Biol Drug Des. 2017 Nov;90(5):943-952. doi: 10.1111/cbdd.13020. Epub 2017 Jun 15.
Twenty-one novel 5-phenyl-1,3,4-oxadiazole-2-thiol (POT) substituted N-hydroxyethyl quaternary ammonium salts (6a-g, 7a-g, 8a-g) were prepared and characterized by FTIR, NMR, and elemental analysis. Compounds 6a, 6c, and 8a were confirmed by X-ray single-crystal diffraction. They display the unsurpassed antibacterial activity against Staphylococcus aureus, α-H-tococcus, Escherichia coli, P. aeruginosa, Proteus vulgaris, Canidia Albicans, especially 6g, 7g, 8g with dodecyl group. Compounds 8a-d with N,N-dihydroxyethyl and POT groups display unsurpassed antibacterial activity and non-toxicity. The structure-activity relationships indicate that POT and flexible dihydroxyethyl group in QAS are necessary for antibacterial activity and cytotoxicity. SEM and TEM images of E. coli morphologies of 8d show the antibacterial agents can adhere to membrane surfaces to inhibit bacterial growth by disrupting peptidoglycan formation and releasing bacterial cytoplasm from cell membranes.
制备了21种新型的5-苯基-1,3,4-恶二唑-2-硫醇（POT）取代的N-羟乙基季铵盐（6a-g、7a-g、8a-g），并通过傅里叶变换红外光谱（FTIR）、核磁共振（NMR）和元素分析对其进行了表征。化合物6a、6c和8a通过X射线单晶衍射得到确证。它们对金黄色葡萄球菌、α-溶血性链球菌、大肠杆菌、铜绿假单胞菌、普通变形杆菌、白色念珠菌表现出无与伦比的抗菌活性，尤其是带有十二烷基的6g、7g、8g。带有N,N-二羟乙基和POT基团的化合物8a-d表现出无与伦比的抗菌活性且无毒。构效关系表明，季铵盐中的POT和柔性二羟乙基基团对抗菌活性和细胞毒性是必需的。8d对大肠杆菌形态的扫描电子显微镜（SEM）和透射电子显微镜（TEM）图像显示，抗菌剂可通过破坏肽聚糖形成并从细胞膜释放细菌细胞质而附着于膜表面以抑制细菌生长。
