Xia Qier, Li Jun, Yang Zhenyu, Zhang Dingguo, Tian Jinjun, Gu Bin
Department of Urology, Shanghai Pudong New Area People's Hospital, Shanghai, China.
Chem Biol Drug Des. 2023 Feb;101(2):271-277. doi: 10.1111/cbdd.14066. Epub 2022 Dec 2.
A novel series of 1,3,5-triazine-phenylthiazole-pyrazole derivatives were synthesized and subsequently tested for Escherichia coli DNA Gyrase inhibitory activity where they showed excellent inhibitory activity. The top-three ranked DNA gyrase inhibitor (4e, 4g and 4h) were further subjected to antibacterial and anti-biofilm activity against clinical isolates of resistant E. coli strains obtained from Urinary Tract Infection (UTI) patients (CREC81, CREC106, CREC163). Compound 4h was identified as most potent antibacterial agent in the above study. The compound 4h was further evaluated in murine model of E. coli UTI in BALB/c mice infected by transurethral injection of CREC106 strain. Results of the study suggest that compound 4h reduces bacterial load of CREC106 in the treated mice and found approximately equipotent to Novobiocin as standard.
合成了一系列新型的1,3,5-三嗪-苯基噻唑-吡唑衍生物，随后对其进行了大肠杆菌DNA促旋酶抑制活性测试，结果显示它们具有优异的抑制活性。排名前三的DNA促旋酶抑制剂（4e、4g和4h）进一步针对从尿路感染（UTI）患者中分离出的耐大肠杆菌临床菌株（CREC81、CREC106、CREC163）进行了抗菌和抗生物膜活性测试。在上述研究中，化合物4h被确定为最有效的抗菌剂。通过经尿道注射CREC106菌株感染BALB/c小鼠，在大肠杆菌UTI小鼠模型中进一步评估了化合物4h。研究结果表明，化合物4h降低了治疗小鼠体内CREC106的细菌载量，发现其与作为标准的新生霉素效力大致相当。
