Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, Yunnan, China.
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, Yunnan, China.
Bioorg Chem. 2022 Feb;119:105494. doi: 10.1016/j.bioorg.2021.105494. Epub 2021 Nov 19.
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 EC values in the range of 0.0508 ∼ 0.0966 μM, 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 EC of compound 4a and 4b against DENV-II (13.2 μM and 9.23 μM, respectively) were better than that of the positive control ribavirin (EC = 40.78 μM). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.
目前，HIV 和 DENV 都是严重威胁人类生命、健康和社会经济的病原体，尚未成功研发出针对 HIV 和 DENV 的疫苗，抗 HIV 或 DENV 药物的研究仍具有重要意义。本研究设计并合成了一系列具有 C6 结构优化的新型 2-芳基-1H-吡唑-S-DABO 类化合物作为有效的 NNRTIs，其中 8 个化合物具有低细胞毒性和在 0.0508∼0.0966 μM 范围内的 EC 值，其选择性指数 SI ＞1415∼3940。特别是，两个化合物 4a 和 4b 被鉴定对四种血清型的 DENV 具有良好的抑制作用。化合物 4a 和 4b 对 DENV-II 的 EC 值（分别为 13.2 μM 和 9.23 μM）优于阳性对照利巴韦林（EC=40.78 μM）。此外，还讨论了 C-6 取代基对这些化合物抗 HIV 或抗 DENV 活性的影响。
