Synthesis and biological evaluation of berberine derivatives as a new class of broad-spectrum antiviral agents against Coxsackievirus B

Bioorg Chem. 2020 Jan:95:103490. doi: 10.1016/j.bioorg.2019.103490. Epub 2019 Dec 9.

Abstract

A series of novel berberine (BBR) analogues were prepared and tested for their antiviral potencies against six different genotype Coxsackievirus B (CVB1-6) strains, taking BBR core for structural modification. Structure-activity relationship (SAR) research revealed that introduction of a primary amine through a linker at position 3 might be beneficial for both antiviral activity and safety. Compound 14c displayed most promising inhibitory potency with IC50 values of 3.08-9.94 µM against tested CVBs 2-6 strains and satisfactory SI value of 34.3 on CVB3, better than that of BBR. Also, 14c could inhibit CVB3 replication through down-regulating the expression of VP1 protein and VP1 RNA. The mechanism revealed that 14c could suppress host components JNK-MAPK, ERK-MAPK and p38-MAPK activation. Therefore, BBR derivatives were considered to be a new class of anti-CVB agents with an advantage of broad-spectrum anti-CVB potency.

Keywords: Berberine; Broad spectrum; Coxsackievirus B; ERK-MAPK; JNK-MAPK; P38-MAPK; Structure-activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Berberine / chemical synthesis
  • Berberine / chemistry
  • Berberine / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Enterovirus B, Human / drug effects*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Berberine