Munir Samman, Khurshid Mohsin, Ahmad Matloob, Ashfaq Usman Ali, Zaki Magdi E A
Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Department of Microbiology, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Pharmaceutics. 2022 Dec 10;14(12):2768. doi: 10.3390/pharmaceutics14122768.
Toward the search for novel antimicrobial agents to control pathogenic -associated infections, a series of novel norfloxacin derivatives were screened for antimicrobial activities. The norfloxacin derivative, 1-ethyl-6-fluoro-7-(4-(2-(2-(3-hydroxybenzylidene)hydrazinyl)-2-oxoethyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (NF22) demonstrated excellent antibacterial activities against ATCC 25922 (MIC = 0.0625 μg/mL) and MDR 1-3 (MIC = 1, 2 and 1 µg/mL). The time-kill kinetic studies have demonstrated that the NF22 was advantageous over norfloxacin and ciprofloxacin in killing the control and MDR strains. The checkerboard assay showed that NF22 in combination with tetracycline had a synergistic effect against the strains. The experimental findings are supported by molecular modeling studies on DNA gyrase, explaining the interactions involved for compound NF22, compared to norfloxacin and ciprofloxacin. Further, the compound was also evaluated for various pharmacokinetics (absorption, metabolism, distribution, toxicity and excretion) as well as drug-likeness properties. Our data have highlighted the potential of norfloxacin by restoring its efficacy against which could lead to the development of new antimicrobial agents.
为了寻找新型抗菌剂以控制与病原体相关的感染，对一系列新型诺氟沙星衍生物进行了抗菌活性筛选。诺氟沙星衍生物1-乙基-6-氟-7-(4-(2-(2-(3-羟基亚苄基)肼基)-2-氧代乙基)哌嗪-1-基)-4-氧代-1,4-二氢喹啉-3-羧酸（NF22）对ATCC 25922（MIC = 0.0625μg/mL）和MDR 1-3（MIC = 1、2和1μg/mL）表现出优异的抗菌活性。时间杀菌动力学研究表明，NF22在杀灭对照菌株和多重耐药菌株方面优于诺氟沙星和环丙沙星。棋盘法试验表明，NF22与四环素联合使用对这些菌株具有协同作用。DNA回旋酶的分子建模研究支持了实验结果，解释了与诺氟沙星和环丙沙星相比，化合物NF22所涉及的相互作用。此外，还对该化合物的各种药代动力学（吸收、代谢、分布、毒性和排泄）以及类药性质进行了评估。我们的数据突出了诺氟沙星通过恢复其对……的疗效而具有的潜力，这可能会导致新型抗菌剂的开发。
