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Synthesis of imidazolidine‐2,4‐dione and 2‐thioxoimidazolidin‐4‐one derivatives as inhibitors of virulence factors production in Pseudomonas aeruginosa
Author(s) -
Mohamed Basant,
AbdelSamii Zakaria K.,
AbdelAal Eatedal H.,
Abbas Hisham A.,
Shaldam Moataz A.,
Ghanim Amany M.
Publication year - 2020
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201900352
Subject(s) - pyocyanin , virulence , pseudomonas aeruginosa , hemolysin , imidazolidine , quorum sensing , microbiology and biotechnology , chemistry , protease , virulence factor , bacteria , enzyme , biology , stereochemistry , biochemistry , gene , genetics
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.