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J Med Chem. 2017 Dec 14;60(23):9821-9837. doi: 10.1021/acs.jmedchem.7b01426. Epub 2017 Nov 27.

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

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College of Pharmacy, Korea University , 2511 Sejong-ro, Jochiwon-eup, Sejong 30019, Republic of Korea.
School of Civil, Environmental and Architectural Engineering, Korea University , 145 Anam-ro, Seongbuk-Gu, Seoul 02841, Republic of Korea.
Division of Magnetic Resonance, Korea Basic Science Institute , 161 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do 28119, Republic of Korea.
Department of Bio-analytical Science, University of Science & Technology , Daejeon 34113, Republic of Korea.
KU-KIST Graduate School of Converging Science and Technology, Korea University , 145 Anam-ro, Seongbuk-Gu, Seoul 02841, Republic of Korea.
Biomedical Research Center, Korea University Guro Hospital , 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea.


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.

[Indexed for MEDLINE]

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