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Design, Synthesis, and Biological Evaluation of Novel Acylhydrazone Derivatives as Potent Neuraminidase Inhibitors.
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2020-08-24 , DOI: 10.1021/acsmedchemlett.0c00313 Meng Li 1 , Li Ping Cheng 1 , Wan Pang 1 , Zhi Jian Zhong 1 , Ling Ling Guo 1
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2020-08-24 , DOI: 10.1021/acsmedchemlett.0c00313 Meng Li 1 , Li Ping Cheng 1 , Wan Pang 1 , Zhi Jian Zhong 1 , Ling Ling Guo 1
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Neuraminidase (NA) is an important target for current research on anti-influenza drugs. The acylhydrazone derivatives containing the −CONHN═CH– framework have been shown to have good NA inhibitory activity. In this paper, a series of novel acylhydrazone NA inhibitors (9a–9n) were designed and synthesized, and the inhibitory activities against NA were evaluated in vitro. The NA inhibition results showed that compound 9j has the most potent inhibitory activity (IC50 = 0.6 μM) against NA, which is significantly lower than that of the positive control oseltamivir carboxylic acid (OSC) (IC50 = 17.00 μM). Molecular docking analysis indicates that the acylhydrazone group plays an important role in compound 9j, which can bind well to the residues Arg371 and Arg292 in the S1 subsite of NA. The good potency of 9j may be also ascribed to the extending of morpholinyl ring into the 430-cavity. The results of this work may contribute to the development of more potent NA inhibitors to against mutant influenza viruses.
中文翻译：
作为强效神经氨酸酶抑制剂的新型酰腙衍生物的设计、合成和生物学评价。
神经氨酸酶（NA）是当前抗流感药物研究的重要靶点。含有-CONHN=CH-骨架的酰腙衍生物已被证明具有良好的NA抑制活性。本文设计合成了一系列新型酰腙NA抑制剂（9a - 9n），并在体外评价了对NA的抑制活性。的NA抑制结果表明，化合物9j中具有最有效的抑制活性（IC 50 = 0.6μM）针对NA，这是显著低于阳性对照奥塞米韦羧酸（OSC）的（IC 50= 17.00 微米）。分子对接分析表明，酰腙基团在化合物9j中起重要作用，可以与NA的S1亚位点的残基Arg371和Arg292很好地结合。9j的良好效力也可归因于吗啉环延伸到 430 腔中。这项工作的结果可能有助于开发更有效的 NA 抑制剂来对抗突变流感病毒。
更新日期：2020-09-10
中文翻译：
作为强效神经氨酸酶抑制剂的新型酰腙衍生物的设计、合成和生物学评价。
神经氨酸酶（NA）是当前抗流感药物研究的重要靶点。含有-CONHN=CH-骨架的酰腙衍生物已被证明具有良好的NA抑制活性。本文设计合成了一系列新型酰腙NA抑制剂（9a - 9n），并在体外评价了对NA的抑制活性。的NA抑制结果表明，化合物9j中具有最有效的抑制活性（IC 50 = 0.6μM）针对NA，这是显著低于阳性对照奥塞米韦羧酸（OSC）的（IC 50= 17.00 微米）。分子对接分析表明，酰腙基团在化合物9j中起重要作用，可以与NA的S1亚位点的残基Arg371和Arg292很好地结合。9j的良好效力也可归因于吗啉环延伸到 430 腔中。这项工作的结果可能有助于开发更有效的 NA 抑制剂来对抗突变流感病毒。
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