Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3690-3. doi: 10.1016/j.bmcl.2015.06.043. Epub 2015 Jun 17.

Abstract

A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' could greatly enhance the antivirus potency. Compared to the lead compounds, the newly synthesized matrinic amide derivatives 21c-d and 21j exhibited stronger anti-CVB3 activities with lower micromolar IC50 from 2.5 μM to 2.7 μM, and better therapeutic properties with improved selectivity index (SI) from 63 to 67. The SAR results provided powerful information for further strategic optimization, and these top compounds were selected for the next evaluation as novel enterovirus inhibitors.

Keywords: Coxsackievirus B3; Enterovirus; Matrinic amide; Matrinic amine; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Chlorocebus aethiops
  • Drug Evaluation, Preclinical / methods
  • Enterovirus B, Human / drug effects*
  • Enterovirus B, Human / pathogenicity
  • Structure-Activity Relationship*
  • Vero Cells / drug effects
  • Vero Cells / virology

Substances

  • Antiviral Agents