1. Synthesis of imidazolidine‐2,4‐dione and 2‐thioxoimidazolidin‐4‐one derivatives as inhibitors of virulence factors production in Pseudomonas aeruginosa
- Author
-
Hisham A. Abbas, Moataz A. Shaldam, Zakaria K. Abdel-Samii, Eatedal H. Abdel-Aal, Amany M. Ghanim, and Basant Mohamed
- Subjects
Virulence Factors ,medicine.medical_treatment ,Pharmaceutical Science ,Virulence ,Imidazolidines ,medicine.disease_cause ,01 natural sciences ,Microbiology ,Hemolysin Proteins ,Structure-Activity Relationship ,chemistry.chemical_compound ,Minimum inhibitory concentration ,Pyocyanin ,Imidazolidine ,Drug Discovery ,medicine ,Protease Inhibitors ,chemistry.chemical_classification ,Protease ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Pseudomonas aeruginosa ,Hemolysin ,0104 chemical sciences ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Enzyme ,chemistry ,Pyocyanine ,Peptide Hydrolases - Abstract
In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudomonas aeruginosa, including protease, hemolysin, and pyocyanin. Imidazolidine-2,4-diones 4c, 4j, and 12a showed complete inhibition of the protease enzyme, and they almost completely inhibited the production of hemolysin at 1/4 MIC (1/4 minimum inhibitory concentration; 1, 0.5, and 0.5 mg/ml, respectively). 2-Thioxoimidazolidin-4-one derivative 7a exhibited the best inhibitory activity (96.4%) against pyocyanin production at 1 mg/ml (1/4 MIC). A docking study was preformed to explore the potential binding interactions with quorum-sensing receptors (LasR and RhlR), which are responsible for the expression of virulence genes.
- Published
- 2020