Computational Design of Azine-Linked Hybrids of 2-Indolinone-Thiazolodine Scaffold as Novel and Promising Quorum Sensing Inhibitors

Microbial multidrug resistance is becoming a global menace to humanity, and finding alternative approaches to combat these "superbugs" is critical. Targeting quorum sensing (QS), which is essential for bacterial biofilm formation and virulence factors production, represents a viable altern...

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Bibliographic Details
Published inPolycyclic aromatic compounds Vol. 44; no. 1; pp. 1 - 24
Main Authors Qayed, Wesam S., Hassan, Mostafa A., Abouwarda, Ahmed Megahed, Ibrahim, Yasser Musa, Aboul-Fadl, Tarek
Format Journal Article
LanguageEnglish
Published Philadelphia Taylor & Francis 02.01.2024
Taylor & Francis Ltd
Subjects
2-Indolinone-thiazolodine
Bacteria
Biofilms
DFT analysis
Hybrids
Inhibitors
Lead compounds
Microorganisms
Molecular docking
molecular hybridization
molecular modeling
Multidrug resistance
Quorum sensing
quorum sensing inhibitors
Scaffolds
Virulence factors
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Summary:Microbial multidrug resistance is becoming a global menace to humanity, and finding alternative approaches to combat these "superbugs" is critical. Targeting quorum sensing (QS), which is essential for bacterial biofilm formation and virulence factors production, represents a viable alternative strategy for combating a variety of diseases. Accordingly, the current work reports potential QS inhibitors (QSIs), which could target the transcriptional regulator protein CviR in the model QS bacterium Chromobacterium violaceum. A set of novel hybrids 4(a-k) were synthesized using the virtual screening results of structurally based hybrids of the 2-indolinone-thiazolidine scaffold on the CviR active pocket residues. The ability of these hybrids to inhibit the QS system was tested against C. violaceum, and two molecules (4h and 4i) revealed promising antivirulence activity. Biofilm formation and motility were both impaired in the treated bacterial cells. Moreover, the molecular docking of these two compounds was comparable with that of chlorolactone (CL), a native inhibitor of the C. violaceum CviR. The global chemical descriptors were calculated for compounds 4h and 4i and found to be more reactive than the native inhibitor, CL. Furthermore, the in silico ADME prediction profiles of these two lead compounds, 4h and 4i, showed good ADME profiles.
ISSN:1040-6638
1563-5333
DOI:10.1080/10406638.2023.2165511