| Title | Computer aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors. | | Author(s) | Yang L, Rybtke MT, Jakobsen TH, Hentzer M, Bjarnsholt T, Givskov M, Tolker-Nielsen T | | Institution | Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark; Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. | | Source | Antimicrob Agents Chemother 2009 Apr 13. | | Abstract | Attenuation of Pseudomonas aeruginosa virulence by use of small molecule quorum-sensing inhibitors (referred to as the anti-pathogenic drug principle) is likely to play a role in future treatment strategies of chronic infections. In this study, structure-based virtual screening was applied in a search for putative quorum-sensing inhibitors from a database comprising approved drugs and natural compounds. The database was built from compounds which showed structural similarities with previously reported quorum-sensing inhibitors, the ligand of the P. aeruginosa quorum-sensing receptor LasR, as well as a quorum-sensing receptor agonist. Six top ranking compounds, all recognized drugs, were identified and tested for quorum-sensing inhibitory activity. Three compounds, salicylic acid, nifuroxazide and chlorzoxazone, showed significant inhibition of quorum-sensing regulated gene expression and related phenotypes in a dose dependant manner. These results suggest that the identified compounds have the potential to be used as anti-pathogenic drugs. Furthermore the results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial infections. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19364871 |
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