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.
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic human pathogen
that forms biofilms and produces virulence factors via quorum sensing (QS). Blocking the QS system in P.
aeruginosa is an excellent strategy to reduce biofilm
formation and the production of virulence factors. RhlR plays an essential
role in the QS system of P. aeruginosa. We synthesized 55 analogues based on the chemical structure of
4-gingerol and evaluated their RhlR inhibitory activities using the
cell-based reporter strain assay. Comprehensive structure–activity
relationship studies identified the alkynyl ketone 30 as the most potent RhlR antagonist. This compound displayed selective
RhlR antagonism over LasR and PqsR, strong inhibition of biofilm formation,
and reduced production of virulence factors in P. aeruginosa. Furthermore, the survival rate of Tenebrio molitor larvae treated with 30
in vivo greatly
improved. Therefore, compound 30, a pure RhlR antagonist,
can be utilized for developing QS-modulating molecules in the control
of P. aeruginosa infections.
Vertically aligned carbon nanotube (VACNT) membranes have attracted significant attention for water purification owing to their ultra-high water permeability and antibacterial properties. In this paper, we critically review the recent progresses in the synthesis of VACNT arrays and fabrication of VACNT membrane methods, with particular emphasis on improving water permeability and anti-biofouling properties. Furthermore, potential applications of VACNT membranes other than water purification (e.g., conductive membranes, electrodes in proton exchange membrane fuel cells, and solar electricity–water generators) have been introduced. Finally, future outlooks are provided to overcome the limitations of commercialization and desalination currently faced by VACNT membranes. This review will be useful to researchers in the broader scientific community as it discusses current and new trends regarding the development of VACNT membranes as well as their potential applications.
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