Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus Mutans Biofilms

J Am Chem Soc. 2017 May 31;139(21):7188-7191. doi: 10.1021/jacs.7b03879. Epub 2017 May 17.

Abstract

The oral microbiome is a dynamic environment inhabited by both commensals and pathogens. Among these is Streptococcus mutans, the causative agent of dental caries, the most prevalent childhood disease. Carolacton has remarkably specific activity against S. mutans, causing acid-mediated cell death during biofilm formation; however, its complex structure limits its utility. Herein, we report the diverted total synthesis and biological evaluation of a rationally designed library of simplified analogs that unveiled three unique biofilm phenotypes further validating the role of natural product synthesis in the discovery of new biological phenomena.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Macrolides / chemical synthesis
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Molecular Structure
  • Particle Size
  • Phenotype
  • Streptococcus mutans / cytology
  • Streptococcus mutans / drug effects*
  • Streptococcus mutans / metabolism
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Biological Products
  • Macrolides
  • carolacton