Repurposing celecoxib analogues as leads for antibiotics

【概述】药物重定位是一种用于发现老药或在研药物超出原始批准的适应症，扩大其适用范围和用途的策略。通过重定位策略提供的先导化合物具有良好的类药性，针对临床确切有效的靶标及具有新的结构类型等优点，能大大缩短新型抗菌药物研究周期并提高开发的成功率。非甾类抗炎药COX-2选择性抑制剂塞来昔布因其药物杂泛性的特点具有较好的抗菌活性引起了研究者的关注。本论文探讨塞来昔布作为抗菌药物开发的可能性。

【期刊名称】Future Medicinal Chemistry

【发表日期】2021.3.30

【论文作者】Baowei Yang, Yicheng Mei, Qianhui Li, Mengyuan Zhang, Huiling Tang, Tong
Liu, Feng Feng, QiyunFu*, Yuzhang Jiang*, Qizhuang Ye*

【论文通讯作者】QiyunFu，Yuzhang Jiang，叶其壮

【论文作者单位】淮安食品药品职业技术学院，南京医科大学淮安第一人民医院，广州明药科技有限公司

【引用信息】Future Med Chemical. 2021 Jun;13(11):959-974. doi: 10.4155/fmc-2021-0030. Epub 2021 Mar 30.

【论文摘要】There is an urgent need for new antibiotics and alternative strategies to combat bacterial pathogens. Molecular docking, antibacterial evaluation in vitro and in vivo, cytotoxicity assessment and enzyme inhibition analyses were performed. Compound 12 exhibited antimicrobial activity against Staphylococcus aureus (MIC: 4 μg/ml), various clinically isolated strains of MRSA (MIC: 4-16 μg/ml) and Acinetobacter baumannii (MIC: 4 μg/ml) when combined with subinhibitory concentrations of colistin B. Compound 12 (20 mg/kg) yielded mild improvement in survival of methicillin-resistant Staphylococcus aureus (MRSA)-infected mice. Additionally, enzyme inhibition tests showed that compound 12 exhibited inhibitory effects against S. aureus dihydrofolate reductase (105.1 μg/ml) and DNA gyrase (122.8 μg/ml). Compound 12 is a promising antibacterial candidate for further development.

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