Abstract
The quorum sensing (QS) enhanced transcriptional regulator SdiA of S. typhimurium is the best known and potential target and responds to a broad range of AHLs and AHL analogs. On the other hand, in many gram-negative bacteria including S. typhimurium, brominated furanones were reported to have inhibitory activity against the QS phenotypes. Motivated by both, we designed an in silico group of halogenated AHLs by substituting halogen compounds (Br, Cl, F and I) on the lactone ring of AHLs and analyzed their interactions with SdiA. The best analogs based on their docking score and another 18 training sets with inhibitory activity against S. typhimurium QS were used to design the pharmacophore. This pharmacophore model was used as a 3D database query against the MayBridge Database consisting of 56,000 compounds and subsequently, the screened compounds were filtered by Lipinski’s rule and ADMET properties. This results in 10 compounds as probable leads to inhibit the SdiA activity and they were docked in the active site of SdiA. Among these, 3 compounds CD01374, RJF00047, and KM10117 exhibited the best docking scores and also favors the necessary hydrogen bond interactions with the essential amino acids in SdiA, and thus identified as novel leads to inhibit Salmonella pathogenicity.
Keywords: Docking, pharmacophore, quorum sensing, Salmonella typhimurium, virtual screening.
Combinatorial Chemistry & High Throughput Screening
Title:Identification of Potent Inhibitors for Salmonella Typhimurium Quorum Sensing via Virtual Screening and Pharmacophore Modeling
Volume: 16 Issue: 10
Author(s): Shanmugam Gnanendra, Syed Mohamed and Jeyakumar Natarajan
Affiliation:
Keywords: Docking, pharmacophore, quorum sensing, Salmonella typhimurium, virtual screening.
Abstract: The quorum sensing (QS) enhanced transcriptional regulator SdiA of S. typhimurium is the best known and potential target and responds to a broad range of AHLs and AHL analogs. On the other hand, in many gram-negative bacteria including S. typhimurium, brominated furanones were reported to have inhibitory activity against the QS phenotypes. Motivated by both, we designed an in silico group of halogenated AHLs by substituting halogen compounds (Br, Cl, F and I) on the lactone ring of AHLs and analyzed their interactions with SdiA. The best analogs based on their docking score and another 18 training sets with inhibitory activity against S. typhimurium QS were used to design the pharmacophore. This pharmacophore model was used as a 3D database query against the MayBridge Database consisting of 56,000 compounds and subsequently, the screened compounds were filtered by Lipinski’s rule and ADMET properties. This results in 10 compounds as probable leads to inhibit the SdiA activity and they were docked in the active site of SdiA. Among these, 3 compounds CD01374, RJF00047, and KM10117 exhibited the best docking scores and also favors the necessary hydrogen bond interactions with the essential amino acids in SdiA, and thus identified as novel leads to inhibit Salmonella pathogenicity.
Export Options
About this article
Cite this article as:
Gnanendra Shanmugam, Mohamed Syed and Natarajan Jeyakumar, Identification of Potent Inhibitors for Salmonella Typhimurium Quorum Sensing via Virtual Screening and Pharmacophore Modeling , Combinatorial Chemistry & High Throughput Screening 2013; 16 (10) . https://dx.doi.org/10.2174/1386207311301010003
DOI https://dx.doi.org/10.2174/1386207311301010003 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers