Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan Xi Li 1#, Beijing 100050, China.
Shandong Xinhua Pharmaceutical Co., Ltd., No. 1, Lu Tai Road, High Tech Zone, Zibo 255199, China.
Bioorg Med Chem Lett. 2020 Apr 15;30(8):126887. doi: 10.1016/j.bmcl.2019.126887. Epub 2019 Dec 13.
A series of new asymmetric bisamidine was designed, synthesized, and tested for their in-vitro antibacterial activity using a range of Gram-positive and Gram-negative pathogens. Most compounds demonstrated powerful antibacterial activity, and interestingly, some displayed better activity against several Gram-negative strains than the lead compound 1. The most potent bisamidine 8l exhibited 4-fold more potent activity against E. coli, K. pneumonia, P. aeruginosa, and C. freundii than compound 1. Especially 8l exhibited a powerful activity against K. pneumonia secreting NDM-1 enzyme with a minimum inhibitory concentration (MIC) of 2 μg/mL, while levofloxacin and vancomycin displayed resistance, with MICs > 128 μg/mL.
一系列新的不对称双脒被设计、合成并测试了它们对一系列革兰氏阳性和革兰氏阴性病原体的体外抗菌活性。大多数化合物表现出强大的抗菌活性，有趣的是，一些化合物对几种革兰氏阴性菌株的活性比先导化合物 1 更好。最有效的双脒 8l 对大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和弗氏柠檬酸杆菌的活性比化合物 1 强 4 倍。特别是 8l 对分泌 NDM-1 酶的肺炎克雷伯菌表现出强大的活性，最小抑菌浓度（MIC）为 2μg/mL，而左氧氟沙星和万古霉素表现出耐药性，MIC>128μg/mL。
