TY  - JOUR
A1  - Barthels, Fabian
A1  - Marincola, Gabriella
A1  - Marciniak, Tessa
A1  - Konhäuser, Matthias
A1  - Hammerschmidt, Stefan
A1  - Bierlmeier, Jan
A1  - Distler, Ute
A1  - Wich, Peter R.
A1  - Tenzer, Stefan
A1  - Schwarzer, Dirk
A1  - Ziebuhr, Wilma
A1  - Schirmeister, Tanja
T1  - Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A
JF  - ChemMedChem
N2  - Staphylococcus aureus is one of the most frequent causes of nosocomial and community‐acquired infections, with drug‐resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active‐site cysteine. A broad series of derivatives were synthesized to derive structure‐activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were found to have single‐digit micromolar Ki values and caused up to a 66 % reduction of S. aureus fibrinogen attachment at an effective inhibitor concentration of 10 μM. This new molecule class exhibited minimal cytotoxicity, low bacterial growth inhibition and impaired sortase‐mediated adherence of S. aureus cells.
KW  - antibiotics
KW  - biofilm
KW  - drug design
KW  - sortase A
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214581
VL  - 15
IS  - 10
SP  - 839
EP  - 850
ER  -