Staphylococcus aureus infections remain as one of the greatest medical challenges worldwide. In the US alone, bloodstream infections caused by S. aureus leading to sepsis and endocarditis account for more than 100,000 patients hospitalized yearly, with mortality rates of 15-50%. Given the exceptionally high impact these infections still have today, it is crucial to develop novel therapies to combat them. One target that has recently received attention is the ArlRS two-component system (TCS), which is responsible for governing S. aureus clumping and virulence factors that are intrinsic to the bacteria’s pathogenicity in the bloodstream. Following an extensive library screen, 3,4’dimethoxyflavone was found to inhibit the ArlRS TCS. A structure activity relationship (SAR) study was conducted using this lead compound, yielding 37 flavone derivatives. The synthesized compounds were all tested for their ability to inhibit the ArlRS TCS as well as their selectivity for this system verses additional regulatory systems in S. aureus. Several compounds showed increased inhibitory activity of the ArlRS system.

Structure activity relationship study of flavone derivative inhibitors of the Staphylococcus aureus ArlRS two-component system

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.