Streptococcus mutans sortase A inhibitory metabolites from the flowers of Sophora japonica

Bioorg Med Chem Lett. 2015 Apr 1;25(7):1394-7. doi: 10.1016/j.bmcl.2015.02.051. Epub 2015 Feb 27.

Abstract

A new maltol derivative (2) along with three known maltol derivative (1) and flavonol glycosides (3 and 4) were isolated from the dried flowers of Sophora japonica. Based upon the results of combined spectroscopic methods, the structure of new compound (2) was determined to be maltol-3-O-(4'-O-cis-p-coumaroyl-6'-O-(3-hydroxy-3-methylglutaroyl))-β-glucopyranoside, an isomer of 1. These compounds strongly inhibited the action of sortase A (SrtA) from Streptococcus mutans, a primary etiologic agent of human dental caries. The onset and magnitude of inhibition of the saliva-induced aggregation in S. mutans treated with compound 2 (4×IC50) were comparable to the behavior of untreated srtA-deletion mutant.

Keywords: Aggregation; Metabolites; Sophora japonica; Sortase A; Streptococcus mutans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacyltransferases / antagonists & inhibitors*
  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • Dose-Response Relationship, Drug
  • Flowers / chemistry*
  • Molecular Conformation
  • Pyrones / chemistry
  • Pyrones / isolation & purification
  • Pyrones / pharmacology*
  • Sophora / chemistry*
  • Streptococcus mutans / drug effects*
  • Streptococcus mutans / growth & development
  • Streptococcus mutans / metabolism
  • Structure-Activity Relationship

Substances

  • Bacterial Proteins
  • Pyrones
  • maltol
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases