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首页> 外文期刊>Journal of Medicinal Chemistry >Discovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68)
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Discovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68)

机译：发现喹啉类似物作为针对肠道病毒D68（EV-D68）的有效抗病毒

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摘要

Enterovirus D68 (EV-D68) is an atypical nonpolio enterovirus that mainly infects the respiratory system of humans, leading to moderate-to-severe respiratory diseases. In rare cases, EV-D68 can spread to the central nervous system and cause paralysis in infected patients, especially young children and immunocompromised individuals. There is currently no approved vaccine or antiviral available for the prevention and treatment of EV-D68. In this study, we aimed to improve the antiviral potency and selectivity of a previously reported EV-D68 inhibitor, dibucaine, through structure activity relationship studies. In total, 60 compounds were synthesized and tested against EV-D68 using the viral cytopathic effect assay. Three compounds 10a, 12a, and 12c were identified to have significantly improved potency (EC50 < 1 mu M) and a high selectivity index (>180) compared with dibucaine against five different strains of EV-D68 viruses. These compounds also showed potent antiviral activity in neuronal cells, such as A172 and SH-SY5Y cells, suggesting they might be further developed for the treatment of both respiratory infection as well as neuronal infection.
机译：肠道病毒D68（EV-D68）是一种非典型nonpolio肠道病毒主要是感染人类的​​呼吸系统，导致中度至严重的呼吸系统疾病。在极少数情况下，EV-D68可以扩散到中枢神经系统并导致受感染的患者瘫痪，特别是幼儿和免疫功能性的个体。目前没有可用于预防和治疗EV-D68的批准疫苗或抗病毒。在这项研究中，我们旨在通过结构活动关系研究改善先前报告的EV-D68抑制剂Dibucaine的抗病毒效力和选择性。总共合成60种化合物并使用病毒细胞病变效应测定对EV-D68进行测试。与Dibucaine对5种不同的EV-D68病毒，鉴定出三种化合物10A，12A和12C具有显着改善的效力（EC50 <1μM）和高选择性指数（> 180）。这些化合物还显示出神经元细胞中有效的抗病毒活性，例如A172和SH-SY5Y细胞，表明它们可以进一步开发用于治疗呼吸道感染以及神经元感染。

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  • 来源
    《Journal of Medicinal Chemistry》 |2019年第8期|共17页
  • 作者

    Musharrafieh Rami; Zhang Jiantao; Tuohy Peter; Kitamura Naoya; Bellampalli Shreya Sai; Hu Yanmei; Khanna Rajesh; Wang Jun;

  • 作者单位

    Univ Arizona Coll Pharm Dept Pharmacol &

    Toxicol Tucson AZ 85721 USA;

    Univ Arizona Coll Pharm Dept Pharmacol &

    Toxicol Tucson AZ 85721 USA;

    Univ Arizona Coll Pharm Dept Pharmacol &

    Toxicol Tucson AZ 85721 USA;

    Univ Arizona Coll Pharm Dept Pharmacol &

    Toxicol Tucson AZ 85721 USA;

    Univ Arizona Dept Pharmacol Coll Med Tucson AZ 85721 USA;

    Univ Arizona Coll Pharm Dept Pharmacol &

    Toxicol Tucson AZ 85721 USA;

    Univ Arizona Dept Pharmacol Coll Med Tucson AZ 85721 USA;

    Univ Arizona Coll Pharm Dept Pharmacol &

    Toxicol Tucson AZ 85721 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药学;
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