Small polar hits against S. aureus: Screening, initial hit optimization and metabolomic studies

Andrew S. T. Lim, Isabel M. Vincent, Michael P. Barrett, Ian Gilbert (Lead / Corresponding author)

Research output: Contribution to journalArticle

60 Downloads (Pure)

Abstract

The global prevalence of antibacterial resistance requires new antibacterial drugs with novel chemical scaffolds and modes of action. It is also vital to design compounds with optimal physicochemical properties to permeate the bacterial cell envelope. We described an approach of combining and integrating whole cell screening and metabolomics into early antibacterial drug discovery using a library of small polar compounds. Whole cell screening of a diverse library of small polar compounds against Staphylococcus aureus gave compound 2. Hit expansion was carried out to determine structure-activity relationships. A selection of compounds from this series, together with other screened active compounds, was subjected to an initial metabolomics study to provide a metabolic fingerprint of the mode of action. It was found that compound 2 and its analogues have a different mode of action from some of the known antibacterial compounds tested. This early study highlighted the potential of whole cell screening and metabolomics in early antibacterial drug discovery. Future works will require improving potency and performing orthogonal studies to confirm the modes of action.

Original languageEnglish
Pages (from-to)19199-19215
Number of pages17
JournalACS Omega
Volume4
Issue number21
Early online date4 Nov 2019
DOIs
Publication statusPublished - 19 Nov 2019

Fingerprint Dive into the research topics of 'Small polar hits against <i>S. aureus</i>: Screening, initial hit optimization and metabolomic studies'. Together they form a unique fingerprint.

  • Cite this