1. Academic Validation
  2. Inhibition of zika virus infection by fused tricyclic derivatives of 1,2,4,5-tetrahydroimidazo[1,5-a]quinolin-3(3aH)-one

Inhibition of zika virus infection by fused tricyclic derivatives of 1,2,4,5-tetrahydroimidazo[1,5-a]quinolin-3(3aH)-one

  • Bioorg Chem. 2020 Nov;104:104205. doi: 10.1016/j.bioorg.2020.104205.
Bin Xu 1 Emily M Lee 2 Angelica Medina 2 Xia Sun 1 Decai Wang 1 Hengli Tang 3 Guo-Chun Zhou 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu 211800, China.
  • 2 Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
  • 3 Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. Electronic address: tang@bio.fsu.edu.
  • 4 School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu 211800, China. Electronic address: gczhou@njtech.edu.cn.
Abstract

Zika virus (ZIKV) Infection represents a significant threat to the global health system, and the search for efficient antivirals to ZIKV remains necessary and urgent. In this study, we extended the exploration of our previously discovered scaffold of 1H-pyrrolo[1,2-c]imidazol-1-one and revealed that two trans isomers of compounds 2 and 7 and one mixture with major trans isomer of compound 3 as novel tetrahydroquinoline-fused imidazolone derivatives are active against ZIKV Infection but they are not virucidal. Western Blot and ELISA analyses of ZIKV NS5 and NS1 further demonstrate that compounds of (±)-2, (±)-3 and (±)-7 act as effective agents against ZIKV Infection. We show that the N10's basicity is not the basic requirement for these compounds' Antiviral activity in the current work. Importantly, tuning of some pharmacophores including substituents at arene can generate promising candidates for anti-ZIKV agents.

Keywords

1H-pyrrolo[1,2-c]imidazol-1-one; Antiviral; Arboviruses; Tetrahydroquinoline-fused imidazolone derivatives; Zika virus.

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