4 research outputs found
Structure–Activity Relationships of 6- and 8‑Gingerol Analogs as Anti-Biofilm Agents
<i>Pseudomonas aeruginosa</i> is a causative agent of
chronic infections in immunocompromised patients. Disruption of quorum
sensing circuits is an attractive strategy for treating diseases associated
with <i>P. aeruginosa</i> infection. In this study, we designed
and synthesized a series of gingerol analogs targeting LasR, a master
regulator of quorum sensing networks in <i>P. aeruginosa</i>. 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 <b>41</b>, an analog of (<i>R</i>)-8-gingerol
with restricted rotation, showed stronger LasR-binding affinity and
inhibition of biofilm formation than the known LasR antagonist (<i>S</i>)-6-gingerol. This new LasR antagonist can be used as an
early lead compound for the development of anti-biofilm agents to
treat <i>P. aeruginosa</i> infections
Structure–Activity Relationships of 6- and 8‑Gingerol Analogs as Anti-Biofilm Agents
<i>Pseudomonas aeruginosa</i> is a causative agent of
chronic infections in immunocompromised patients. Disruption of quorum
sensing circuits is an attractive strategy for treating diseases associated
with <i>P. aeruginosa</i> infection. In this study, we designed
and synthesized a series of gingerol analogs targeting LasR, a master
regulator of quorum sensing networks in <i>P. aeruginosa</i>. 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 <b>41</b>, an analog of (<i>R</i>)-8-gingerol
with restricted rotation, showed stronger LasR-binding affinity and
inhibition of biofilm formation than the known LasR antagonist (<i>S</i>)-6-gingerol. This new LasR antagonist can be used as an
early lead compound for the development of anti-biofilm agents to
treat <i>P. aeruginosa</i> infections
Structure–Activity Relationships of 6- and 8‑Gingerol Analogs as Anti-Biofilm Agents
<i>Pseudomonas aeruginosa</i> is a causative agent of
chronic infections in immunocompromised patients. Disruption of quorum
sensing circuits is an attractive strategy for treating diseases associated
with <i>P. aeruginosa</i> infection. In this study, we designed
and synthesized a series of gingerol analogs targeting LasR, a master
regulator of quorum sensing networks in <i>P. aeruginosa</i>. 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 <b>41</b>, an analog of (<i>R</i>)-8-gingerol
with restricted rotation, showed stronger LasR-binding affinity and
inhibition of biofilm formation than the known LasR antagonist (<i>S</i>)-6-gingerol. This new LasR antagonist can be used as an
early lead compound for the development of anti-biofilm agents to
treat <i>P. aeruginosa</i> infections
Colour and behavioural data, Activity level survey data, and predation experiments data file
Colour and behavioural data, Activity level survey data, and predation experiments data fil