2. Academic Validation
  3. 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

  • Bioorg Chem. 2022 Feb;119:105494. doi: 10.1016/j.bioorg.2021.105494.
Ruo-Mei Rui 1,  Cheng-Run Tang 2,  Chun-Tao Zhang 3,  Wen-Kai Pan 1,  Kai Gan 1,  Rong-Hua Luo 3,  Zi-Qian Wei 1,  Fan-Shun Jing 1,  Si-Ming Huang 1,  Liu-Meng Yang 3,  Yi-Ming Li 1,  Yue-Ping Wang 1,  Wei-Lie Xiao 1,  Hong-Bing Zhang 4,  Yong-Tang Zheng 5,  Yan-Ping He 6
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 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. Electronic address: [email protected].
  • 5 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. Electronic address: [email protected].
  • 6 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. Electronic address: [email protected].
PMID: 34836643 DOI: 10.1016/j.bioorg.2021.105494
Abstract

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.

Keywords

Antiviral activity; HIV-1; NNRTIs; S-DABOs, DENV; SAR.

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