Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, United States.
Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, E41013 Seville, Spain.
Bioorg Med Chem Lett. 2019 Jun 1;29(11):1399-1402. doi: 10.1016/j.bmcl.2019.03.032. Epub 2019 Mar 23.
Carbapenemase-producing Enterobacteriaceae (CPE) represents the most worrisome evolution of the antibiotic resistance crisis, which is almost resistant to most of available antibiotics. This situation is getting even worse particularly due to the recent emergence of colistin resistance. Herein, niclosamide, an FDA-approved traditional drug, and its novel O-alkylamino-tethered derivatives were discovered as new and potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Among these molecules, compound 10 (HJC0431) with 4-aminobutyl moiety showed the broad antibacterial activities, effective against 6 strains. In vitro checkerboard and time-kill course studies demonstrated the synergistic effects of the screened compounds with colistin against the corresponding strains with various degrees.
产碳青霉烯酶肠杆菌科（CPE）代表了抗生素耐药危机最令人担忧的演变，几乎对大多数可用的抗生素都具有耐药性。由于最近出现了多粘菌素耐药性，这种情况变得更加糟糕。在此，尼氯硝唑，一种 FDA 批准的传统药物，及其新型的 O-烷基氨基连接的衍生物被发现是针对产碳青霉烯酶和/或多粘菌素耐药肠杆菌科分离株的新型强效抗菌药物。在这些分子中，具有 4-氨基丁基部分的化合物 10（HJC0431）显示出广谱的抗菌活性，有效对抗 6 株菌。体外棋盘和时间杀伤过程研究表明，筛选出的化合物与多粘菌素对不同程度的相应菌株具有协同作用。
