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Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2021 Nov 24; Vol. 26 (23). Date of Electronic Publication: 2021 Nov 24. - Publication Year :
- 2021
-
Abstract
- Staphylococcus aureus ( S. aureus ) is a causative agent of many hospital- and community-acquired infections with the tendency to develop resistance to all known antibiotics. Therefore, the development of novel antistaphylococcal agents is of urgent need. Sortase A is considered a promising molecular target for the development of antistaphylococcal agents. The main aim of this study was to identify novel sortase A inhibitors. In order to find novel antistaphylococcal agents, we performed phenotypic screening of a library containing 15512 compounds against S. aureus ATCC43300. The molecular docking of hits was performed using the DOCK program and 10 compounds were selected for in vitro enzymatic activity inhibition assay. Two inhibitors were identified, N,N-diethyl-N'-(5-nitro-2-(quinazolin-2-yl)phenyl)propane-1,3-diamine ( 1 ) and acridin-9-yl-(1 H -benzoimidazol-5-yl)-amine ( 2 ), which decrease sortase A activity with IC <subscript>50</subscript> values of 160.3 µM and 207.01 µM, respectively. It was found that compounds 1 and 2 possess antibacterial activity toward 29 tested multidrug resistant S. aureus strains with MIC values ranging from 78.12 to 312.5 mg/L. These compounds can be used for further structural optimization and biological research.
- Subjects :
- Aminoacyltransferases genetics
Anti-Bacterial Agents therapeutic use
Bacterial Proteins genetics
Cysteine Endopeptidases genetics
Enzyme Inhibitors chemistry
Humans
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Molecular Docking Simulation
Staphylococcal Infections microbiology
Staphylococcus aureus enzymology
Staphylococcus aureus pathogenicity
Aminoacyltransferases antagonists & inhibitors
Bacterial Proteins antagonists & inhibitors
Enzyme Inhibitors pharmacology
Staphylococcal Infections drug therapy
Staphylococcus aureus drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 26
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 34885677
- Full Text :
- https://doi.org/10.3390/molecules26237095