Dataset Information

Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A.

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-(1H-benzoimidazol-5-yl)-amine (2), which decrease sortase A activity with IC50 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.

SUBMITTER: Volynets G

PROVIDER: S-EPMC8658998 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A.

Volynets Galyna G Vyshniakova Hanna H Nitulescu Georgiana G Nitulescu George Mihai GM Ungurianu Anca A Margina Denisa D Moshynets Olena O Bdzhola Volodymyr V Koleiev Ihor I Iungin Olga O Tarnavskiy Sergiy S Yarmoluk Sergiy S

Molecules (Basel, Switzerland) 20211124 23

<i>Staphylococcus aureus</i> (<i>S. aureus</i>) 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 perfo ...[more]

PMID: 34885677

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Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A.

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Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A.

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