Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing
Compounds which modulate quorum sensing in quorum sensing bacteria. Compounds of the invention inhibit quorum sensing and/or activate quorum sensing in various bacteria. Compounds that inhibit quorum sensing are particularly useful for inhibition of detrimental bacterial biofilm formation. Compounds that activate quorum sensing are particularly useful for promoting growth and biofilm formation of beneficial bacterial.
1. A compound of formula:
A—CO—CH 2 —CO—NH—[CH 2 ] p2 -HG
or a pharmaceutically acceptable salt or ester thereof
where:
p2 is 1 or 2;
A is an unsubstituted alkyl or alkenyl group having 4-10 carbon atoms; and
HG is a phenyl group substituted with one or more substituents selected from the group consisting of halogen, nitro, hydroxyl, nitrile, azide, —R, or —OR wherein R is an alkyl group having 1-6 carbon atoms.
2. The compound of claim 1 wherein HG is a phenyl group substituted with one or more substituents selected from the group consisting of fluorine, nitro, nitrile, azide, —R, or —OR wherein R is an alkyl group having 1-6 carbon atoms.
3. The compound of claim 1 wherein p2 is 1.
4. The compound of claim 1 wherein A is an unsubstituted alkyl group having 4-10 carbon atoms.
5. A compound represented by formula:
or a pharmaceutically acceptable salt or ester thereof
wherein HG is a phenyl group optional substituted with one or more non-hydrogen substituents selected from the group consisting of halogen, nitro, azide, alkyl having 1-3 carbon atoms, haloalkyl having 1-3 carbon atoms, alkoxy having 1-3 carbon atoms, and p2 is 1 or 2.
6. The compound of claim 5 represented by formula:
7. The compound of claim 5 which has formula:
8. A pharmaceutical composition comprising one or more compounds of claim 1 and a pharmaceutically acceptable carrier.
9. The composition of claim 8 further comprising an antimicrobial compound, an antibacterial compound, an antiviral agent or an antibiotic.
10. A method for inhibiting of quorum sensing in bacteria which comprising the step of contacting the quorum sensing bacteria with an amount of a quorum sensing compound of claim 1 effective for inhibiting of quorum sensing.
11. A method for disruption of bacterial biofilm formation which comprises the step of contacting the biofilm or an environment containing the biofilm with one or more compounds of claim 1 .