C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity

• Published in: Bioorganic chemistry Vol. 119; p. 105494
• Main Authors: Rui, Ruo-Mei, Tang, Cheng-Run, Zhang, Chun-Tao, Pan, Wen-Kai, Gan, Kai, Luo, Rong-Hua, Wei, Zi-Qian, Jing, Fan-Shun, Huang, Si-Ming, Yang, Liu-Meng, Li, Yi-Ming, Wang, Yue-Ping, Xiao, Wei-Lie, Zhang, Hong-Bing, Zheng, Yong-Tang, He, Yan-Ping
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.02.2022; Elsevier
• Subjects: Antiviral activity; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Dengue Virus - drug effects; Dose-Response Relationship, Drug; HIV-1; HIV-1 - drug effects; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Molecular Structure; NNRTIs; Physical Sciences; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; S-DABOs, DENV; SAR; Science & Technology; Structure-Activity Relationship; HIV-1; S-DABOs, DENV; SAR; NNRTIs; Antiviral activity; DENGUE; REVERSE-TRANSCRIPTASE INHIBITORS
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105494

[Display omitted] •Developed a series of novel 2-aryl-1H-pyrazole-S-DABOs with 0.0508–0.8375 µM activity against HIV-1.•HIV-1 reverse transcriptase activity assay indicating that HIV RT is the potential target.•Compounds 4a and 4b were identified to have good inhibitory effects on four serotypes of DENV.•Preliminary SAR, especially the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these novel congeners were investigated. 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 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 EC50 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 (EC50 = 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.