Structure-Activity Relationships of 6- and 8-Gingerol Analogs as Anti-Biofilm Agents
| Autor: | Eunji Cha, Jeong Kyu Bang, Youngjoo Byun, Hee Deung Park, Han Shin Kim, So Young Ham, Yujin Shin, Sang Hyun Son, Hyunsuk Choi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Catechols medicine.disease_cause 01 natural sciences Microbiology 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Drug Discovery medicine Humans Pseudomonas Infections 010405 organic chemistry Chemistry Pseudomonas aeruginosa Gingerol Biofilm Antagonist Master regulator Quorum Sensing biochemical phenomena metabolism and nutrition 0104 chemical sciences Anti-Bacterial Agents Molecular Docking Simulation Quorum sensing 030104 developmental biology Biofilms Trans-Activators Molecular Medicine Fatty Alcohols Lead compound Anti biofilm |
| Zdroj: | Journal of medicinal chemistry. 60(23) |
| ISSN: | 1520-4804 |
| Popis: | Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a master regulator of quorum sensing networks in P. aeruginosa. Structure-activity relationship studies showed that a hydrogen-bonding interaction in the head section, stereochemistry and rotational rigidity in the middle section, and optimal alkyl chain length in the tail section are important factors for the enhancement of LasR-binding affinity and for the inhibition of biofilm formation. The most potent compound 41, an analog of (R)-8-gingerol with restricted rotation, showed stronger LasR-binding affinity and inhibition of biofilm formation than the known LasR antagonist (S)-6-gingerol. This new LasR antagonist can be used as an early lead compound for the development of anti-biofilm agents to treat P. aeruginosa infections. |
| Databáze: | OpenAIRE |
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