C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity
C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity
复制标题
2-芳基-1H-吡唑-S-DABO 的 C6 结构优化：从抗 HIV 活性到抗 DENV 活性。
DOI：
10.1016/j.bioorg.2021.105494
复制
发表时间：
2022-01-25
影响因子：
5.1
通讯作者：
He, Yan-Ping
中科院分区：
文献类型：
--
作者：
Rui, Ruo-Mei;Tang, Cheng-Run;He, Yan-Ping
艾滋病病毒和登革病毒是当今人类生命、健康和社会经济的严重威胁。到目前为止，还没有成功开发出针对HIV或DENV的疫苗。抗HIV或DENV药物的研究仍具有重要意义。本研究通过C6结构优化，合成了一系列2-芳基-1H-吡唑-S-DABO化合物，其中8个化合物具有较低的细胞毒性，EC_（50）在0.0508 - 0.0966 μ M之间，选择性指数SI > 1415 - 3940。特别地，两个化合物4a和4 b被鉴定为对四种血清型的DENV具有良好的抑制作用。化合物4a和4 b对DENV-II的EC 50（分别为13.2 μ M和9.23 μ M）优于阳性对照利巴韦林（EC 50 = 40.78 μ M）。此外，还讨论了C-6位取代基对化合物抗HIV或抗DENV活性的影响。
Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The research on anti-HIV or DENV drugs is still of great significance. In this study we developed a series of novel 2-Aryl-1H-pyrazole-S-DABOs with C6-strucutral optimizations as potent NNRTIs, among which, 8 compounds had low cytotoxicity and EC50 values in the range of 0.0508 -0.0966 mu M, and their selectivity index was SI > 1415 -3940. In particular, two compounds 4a and 4b were identified to have good inhibitory effects on DENV of four serotypes. The EC50 of compound 4a and 4b against DENV-II (13.2 mu M and 9.23 mu M, respectively) were better than that of the positive control ribavirin (EC50 = 40.78 mu M). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.