Stefan Hinsberger

TL;DR: It can be expected that combination therapies, also containing antivirulence agents, will pave the way toward novel treatment options against P. aeruginosa, and antivirulent drugs are expected to yield a significantly reduced rate of resistance development.

TL;DR: In vitro testing revealed high inhibitory potencies toward human placental 17β-HSD1, and the most promising compounds, 14 and 15, showed IC(50) values in the low nanomolar range in the cell-free and cellular assays, which make these inhibitors interesting candidates for further preclinical evaluation.

TL;DR: Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between σ(70) and the RNAP core enzyme, which results in lower resistance frequencies compared to clinically used rifampicin.

TL;DR: The most interesting compound of this study was the 3-Cl substituted compound 5 which strongly inhibits PqsD (IC₅₀ 6.2 μM) while exhibiting no inhibition of RNAP.

TL;DR: Highly selective compounds (11, 12, 14, 21 and 22) have been identified, the most promising one (12) showing an IC(50) value in the low nanomolar range (101 nM) and a selectivity factor of 13 toward 17β-HSD1 and an interesting candidate for further biological evaluation.