Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors
| Autor: | Daniel S. Wenholz, Aditi Taunk, Nripendra Nath Biswas, Basmah Almohaywi, Shashidhar Nizalapur, Scott A. Rice, Kitty K. K. Ho, David StC. Black, Renate Griffith, Naresh Kumar, George Iskander |
|---|---|
| Přispěvatelé: | Singapore Centre for Environmental Life Sciences Engineering |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pharmaceutical Science Gene Expression Acyl-Butyrolactones medicine.disease_cause 01 natural sciences Reductive amination Protein Structure Secondary Analytical Chemistry chemistry.chemical_compound Drug Discovery mucobromic acid Amination biology Pseudomonas Aeruginosa Quorum Sensing Anti-Bacterial Agents Molecular Docking Simulation Biochemistry lactam Chemistry (miscellaneous) Pseudomonas aeruginosa Molecular Medicine Oxidation-Reduction Protein Binding Lactams Homoserine Microbial Sensitivity Tests Article lcsh:QD241-441 03 medical and health sciences Structure-Activity Relationship lcsh:Organic chemistry Bacterial Proteins medicine quorum sensing mucochloric acid Protein Interaction Domains and Motifs Pyrroles Physical and Theoretical Chemistry Furans 010405 organic chemistry Organic Chemistry Pathogenic bacteria biology.organism_classification Mucobromic acid 0104 chemical sciences Quorum sensing 030104 developmental biology chemistry Docking (molecular) Drug Design Trans-Activators Bacteria |
| Zdroj: | Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry Molecules, Vol 23, Iss 5, p 1106 (2018) Molecules; Volume 23; Issue 5; Pages: 1106 |
| ISSN: | 1420-3049 |
| Popis: | © 2018 by the authors. Bacterial infections, particularly hospital-acquired infections caused by Pseudomonas aeruginosa, have become a global threat with a high mortality rate. Gram-negative bacteria including P. aeruginosa employ N-acyl homoserine lactones (AHLs) as chemical signals to regulate the expression of pathogenic phenotypes through a mechanism called quorum sensing (QS). Recently, strategies targeting bacterial behaviour or QS have received great attention due to their ability to disarm rather than kill pathogenic bacteria, which lowers the evolutionary burden on bacteria and the risk of resistance development. In the present study, we report the design and synthesis of N-alkyl- and N-aryl 3,4 dichloro- and 3,4-dibromopyrrole-2-one derivatives through the reductive amination of mucochloric and mucobromic acid with aliphatic and aromatic amines. The quorum sensing inhibition (QSI) activity of the synthesized compounds was determined against a P. aeruginosa MH602 reporter strain. The phenolic compounds exhibited the best activity with 80% and 75% QSI at 250 µM and were comparable in activity to the positive control compound Fu-30. Computational docking studies performed using the LasR receptor protein of P. aeruginosa suggested the importance of hydrogen bonding and hydrophobic interactions for QSI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |