Virtual screening for novel quorum sensing inhibitors to eradicate biofilm formation of Pseudomonas aeruginosa

2008 ◽  
Vol 79 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Zhirui Zeng ◽  
Li Qian ◽  
Lixiang Cao ◽  
Hongming Tan ◽  
Yali Huang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Quorum Sensing Inhibitors

scholarly journals Computer-Aided Identification of Recognized Drugs as Pseudomonas aeruginosa Quorum-Sensing Inhibitors

2009 ◽  
Vol 53 (6) ◽  
pp. 2432-2443 ◽  
Author(s):  
Liang Yang ◽  
Morten Theil Rybtke ◽  
Tim Holm Jakobsen ◽  
Morten Hentzer ◽  
Thomas Bjarnsholt ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Bacterial Infections ◽  
Treatment Strategies ◽  
Significant Inhibition ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Quorum Sensing Inhibitors ◽  
Regulated Gene Expression

ABSTRACT Attenuation of Pseudomonas aeruginosa virulence by the use of small-molecule quorum-sensing inhibitors (referred to as the antipathogenic drug principle) is likely to play a role in future treatment strategies for chronic infections. In this study, structure-based virtual screening was used 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 to previously reported quorum-sensing inhibitors, the ligand of the P. aeruginosa quorum-sensing receptor LasR, and 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-dependent manner. These results suggest that the identified compounds have the potential to be used as antipathogenic drugs. Furthermore, the results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial infections.

scholarly journals Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of Pseudomonas aeruginosa

2019 ◽  
Author(s):  
Zulkar Nain ◽  
Sifat Bin Sayed ◽  
Mohammad Minnatul Karim ◽  
Md. Ariful Islam ◽  
Utpal Kumar Adhikari
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Vital Role ◽  
Energy Calculation ◽  
Quorum Sensing Inhibitors ◽  
Binding Energy Calculation ◽  
Standard Precision

Pseudomonas aeruginosa is an emerging opportunistic pathogen responsible for cystic fibrosis and nosocomial infections. In addition, empirical treatments are become inefficient due to their multiple-antibiotic resistance and extensive colonizing ability. Quorum sensing (QS) plays a vital role in the regulation of virulence factors in P. aeruginosa. Attenuation of virulence by QS inhibition could be an alternative and effective approach to control infections. Therefore, we sought to discover new QS inhibitors (QSIs) against LasR receptor in P. aeruginosa using chemoinformatics. Initially, a structure-based high-throughput virtual screening was performed using the LasR active site that identified 61404 relevant molecules. E-pharmacophore (ADAHH) screening of these molecules rendered 72 QSI candidates. In standard-precision docking, only 7 compounds were found as potential QSIs due to their higher binding affinity to LasR receptor (-7.53 to -10.32 kcal/mol compared to -7.43 kcal/mol of native ligands). The ADMET properties of these compounds were suitable to be QSIs. Later, extra-precision docking and binding energy calculation suggested ZINC19765885 and ZINC72387263 as the most promising QSIs. The dynamic simulation of the docked complexes showed good binding stability and molecular interactions. The current study suggested that these two compounds could be used in P. aeruginosa QS inhibition to combat bacterial infections.

Structure based virtual screening for identification of potential quorum sensing inhibitors against LasR master regulator in Pseudomonas aeruginosa

2017 ◽  
Vol 107 ◽  
pp. 136-143 ◽  
Author(s):  
Manmohit Kalia ◽  
Pradeep Kumar Singh ◽  
Vivek Kumar Yadav ◽  
Birendra Singh Yadav ◽  
Deepmala Sharma ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Master Regulator ◽  
Quorum Sensing Inhibitors

Inhibition of quorum sensing-controlled biofilm formation in Pseudomonas aeruginosa by quorum-sensing inhibitors

2017 ◽  
Vol 111 ◽  
pp. 99-107 ◽  
Author(s):  
Ellappan Kalaiarasan ◽  
Kottha Thirumalaswamy ◽  
Belgode Narasimha Harish ◽  
Vasuki Gnanasambandam ◽  
Veeresh Kumar Sali ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Quorum Sensing Inhibitors

Energy-optimized pharmacophore coupled virtual screening in the discovery of quorum sensing inhibitors of LasR protein of Pseudomonas aeruginosa

2019 ◽  
Vol 38 (18) ◽  
pp. 5374-5388 ◽  
Author(s):  
Zulkar Nain ◽  
Sifat Bin Sayed ◽  
Mohammad Minnatul Karim ◽  
Md Ariful Islam ◽  
Utpal Kumar Adhikari
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Quorum Sensing Inhibitors

scholarly journals Benzo[d]thiazole-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl as potent selective lasB quorum sensing inhibitors of Gram-negative bacteria

RSC Advances ◽  
2021 ◽  
Vol 11 (46) ◽  
pp. 28797-28808
Author(s):  
Tung Truong Thanh ◽  
Huy Luong Xuan ◽  
Thang Nguyen Quoc
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Quorum Sensing Inhibitors

Benzo[d]thiazole-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl as potent selective lasB quorum sensing inhibitors and anti-biofilm formation of Pseudomonas aeruginosa.

Quorum Sensing – A Stratagem for Conquering Multi-Drug Resistant Pathogens

2020 ◽  
Vol 26 ◽  
Author(s):  
Madison Tonkin ◽  
Shama Khan ◽  
Mohmmad Younus Wani ◽  
Aijaz Ahmad
Keyword(s):  
Drug Resistance ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Cell Communication ◽  
Natural Compounds ◽  
Quorum Sensing Inhibitors ◽  
Communication Technique ◽  
Multicellular Organisms ◽  
Chemical Strategies

: Quorum sensing is defined as cell to cell communication between microorganisms, which enables microorganisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing as well as biofilm formation encourage the development of drug resistance in microorganisms. Biofilm formation and quorum sensing are causally linked to each other and play role in the pathogenesis of microorganisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the microorganisms. This review encompasses the communication technique used by microorganisms, how microorganism resistance is linked to quorum sensing and various chemical strategies to combat quorum sensing and thereby drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds present several related disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that anti-quorum sensing compounds are effective in disrupting quorum sensing and could therefore be effective in reducing microorganism drug resistance.

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