Structure-Activity Relationships of 6- and 8-Gingerol Analogs as Anti-Biofilm Agents

Hyunsuk Choi, So Young Ham, Eunji Cha, Yujin Shin, Han Shin Kim, Jeong Kyu Bang, Sang Hyun Son, Hee-Deung Park, Youngjoo Byun

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9821-9837
Number of pages17
JournalJournal of Medicinal Chemistry
Volume60
Issue number23
DOIs
Publication statusPublished - 2017 Dec 14

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Choi, H., Ham, S. Y., Cha, E., Shin, Y., Kim, H. S., Bang, J. K., Son, S. H., Park, H-D., & Byun, Y. (2017). Structure-Activity Relationships of 6- and 8-Gingerol Analogs as Anti-Biofilm Agents. Journal of Medicinal Chemistry, 60(23), 9821-9837. https://doi.org/10.1021/acs.jmedchem.7b01426