2. Academic Validation
  3. Synthesis and pharmacodynamic evaluation of 2-aminoindole derivatives against influenza A virus in vitro/vivo

Synthesis and pharmacodynamic evaluation of 2-aminoindole derivatives against influenza A virus in vitro/vivo

  • Eur J Med Chem. 2025 Jan 5:281:117044. doi: 10.1016/j.ejmech.2024.117044.
Zhongmou Zhang 1,  Nanfang Wang 2,  Jiejie Lu 1,  Ying Qu 1,  Yihui Song 3,  Xinyu Yang 3,  Zhanyong Wei 4,  Qi Zhang 3,  Piet Herdewijn 5,  Junbiao Chang 6,  Xiao-Na Wang 7,  Zhenya Wang 8
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, Zhengzhou University, Zhengzhou, 450001, China.
  • 2 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou, 450001, China.
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 4 International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengdong New District Longzi Lake 15#, Zhengzhou 450046, China.
  • 5 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
  • 6 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: changjunbiao@zzu.edu.cn.
  • 7 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou, 450001, China. Electronic address: wangxn@zzu.edu.cn.
  • 8 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, Zhengzhou University, Zhengzhou, 450001, China; International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengdong New District Longzi Lake 15#, Zhengzhou 450046, China; XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: zhenyawang@zzu.edu.cn.
PMID: 39547081 DOI: 10.1016/j.ejmech.2024.117044
Abstract

Influenza Virus is a kind of respiratory pathogen with high morbidity and mortality, which still threatens human health. Existing anti-influenza drugs have various limitations, such as the inability to alleviate body injury and side effects. There remains an urgent need to develop a novel Antiviral drug to efficiently inhibit viral Infection while avoiding body injury. A series of 2-aminoindole derivatives were synthesized via the TMSOTf-catalyzed reactions of N-arylynamides with sulfilimines and evaluated for their anti-influenza virus activity. The experimental results showed that 2-aminoindole 3h had significant Antiviral activity (EC50 = 8.37 ± 0.65 μM) and the lowest cytotoxicity (CC50 = 669.26 ± 11.42 μM) in vitro. 2-Aminoindole 3h could inhibit viral replication by effectively binding to RNA-dependent RNA polymerase (RdRp), and could also directly target host cells to inhibit cytokine storms and Apoptosis induced by viral Infection, thereby improving host cell survival rate. In addition, viral load and organ injury in the lung tissue of infected mice were effectively reduced by 2-aminoindole 3h with satisfactory biosafety. These findings highlight the potential of a valuable therapeutic option against influenza Infection while also laying the foundation for further research and development in this area.

Keywords

2-Aminoindole derivatives; Antiviral; Apoptosis; Cytokine storm; Influenza A virus; Lung injury.

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