新型诺氟沙星-1,3,4-噁二唑杂合子的设计与合成及其作为抗耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌剂。
Design and synthesis of new norfloxacin-1,3,4-oxadiazole hybrids as antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).
机构信息
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, No. 100, KeXue Avenue, Zhengzhou 450001, Henan Province, PR China.
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, No. 100, KeXue Avenue, Zhengzhou 450001, Henan Province, PR China.
出版信息
Eur J Pharm Sci. 2019 Aug 1;136:104966. doi: 10.1016/j.ejps.2019.104966. Epub 2019 Jun 21.
Toward the search of new antibacterial agents to control methicillin-resistant Staphylococcus aureus (MRSA), a class of new norfloxacin-1,3,4-oxadiazole hybrids were designed and synthesized. Antibacterial activities against drug-sensitive bacteria S. aureus and clinical drug resistant isolates of MRSA were evaluated. Compound 5k exhibited excellent antibacterial activities against S. aureus (MIC: 2 μg/mL) and MRSA1-3 (MIC: 0.25-1 μg/mL). The time-kill kinetics demonstrated that compound 5k had an advantage over commonly used antibiotics vancomycin in killing S. aureus and MRSA. Moreover, compound 5k could inhibit the bacteria and destroy their membranes in a short time, and showed very low cytotoxicity to NRK-52E cells. Some interesting structure-activity relationships (SARs) were also discussed. These results indicated that these norfloxacin-1,3,4-oxadiazole hybrids could be further developed into new antibacterial agents against MRSA.
为了寻找新的抗菌剂来控制耐甲氧西林金黄色葡萄球菌（MRSA），设计并合成了一类新型的诺氟沙星-1,3,4-噁二唑杂合化合物。评估了这些化合物对药敏性金黄色葡萄球菌和临床耐药 MRSA 分离株的抗菌活性。化合物 5k 对金黄色葡萄球菌（MIC：2μg/mL）和 MRSA1-3（MIC：0.25-1μg/mL）具有优异的抗菌活性。时间杀伤动力学研究表明，化合物 5k 在杀灭金黄色葡萄球菌和 MRSA 方面优于常用抗生素万古霉素。此外，化合物 5k 可以在短时间内抑制细菌并破坏其细胞膜，并且对 NRK-52E 细胞的细胞毒性非常低。还讨论了一些有趣的构效关系（SARs）。这些结果表明，这些诺氟沙星-1,3,4-噁二唑杂合化合物可以进一步开发成针对 MRSA 的新型抗菌剂。
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