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  3. Synthesis and pharmacodynamic evaluation of naphthalene derivatives against influenza A virus in vitro and in vivo

Synthesis and pharmacodynamic evaluation of naphthalene derivatives against influenza A virus in vitro and in vivo

  • Eur J Med Chem. 2023 Nov 5;259:115660. doi: 10.1016/j.ejmech.2023.115660.
Yongzhuang Ge 1,  Chaofeng Zhang 1,  Ying Qu 1,  Lixia Ding 1,  Xinbo Zhang 1,  Zhongmou Zhang 1,  Chengyun Jin 1,  Xiao-Na Wang 2,  Zhenya Wang 3
Affiliations

Affiliations

  • 1 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 2 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: wangxn@zzu.edu.cn.
  • 3 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address: zhenyawang@zzu.edu.cn.
PMID: 37517205 DOI: 10.1016/j.ejmech.2023.115660
Abstract

Influenza A virus is a highly mutable pathogenic pathogen that could cause a global pandemic. It is necessary to find new anti-influenza drugs to resist influenza epidemics due to the seasonal popularity of a certain area every year. Naphthalene derivatives had potential Antiviral activity. A series of naphthalene derivatives were synthesized via the metal-free intramolecular hydroarylation reactions of alkynes. Evaluation of their biological efficacy showed that compound 2-aminonaphthalene 4d had better Antiviral activity in vitro than ribavirin. By studying the mechanism of action of 2-aminonaphthalene 4din vivo and in vitro, we found that 4d had Antiviral activity to three different subtype influenza viruses of A/Weiss/43 (H1N1), A/Virginia/ATCC2/2009 (H1N1) and A/California/2/2014 (H3N2). Compound 4d had the best effect after viral adsorption, and mainly played in the early stage of virus replication. 2-Aminonaphthalene 4d could reduce the replication of virus by inhibiting the NP and M proteins of virus. Compound 4d cut down ROS accumulation, Autophagy and Apoptosis induced by Influenza Virus. Inflammatory response mediated by RIG-1 pathway were suppressed in the cell and mice. In addition, the pathological changes of lung tissue and virus titer in mice were reduced by the administration of 4d. Therefore, naphthalene derivative 4d is a potential drug for the treatment of influenza A virus Infection.

Keywords

Antiviral activity; Apoptosis; Autophagy; Cytokines; Influenza A virus; Naphthalene derivatives.

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