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US 8,952,192 B2Granted
Phosphorylated and branched dihydroxy-pentane-dione (DPD) analogs as quorum sensing inhibitors in bacteria
AssigneeUniversity of Maryland, College Park
InventorsHerman O. Sintim, William E. Bentley, Varnika Roy, Jacqueline Smith, Reza Ghodssi, Mariana Tsacoumis Meyer
Life of this patent
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Abstract
Provided are compositions and methods for modulating quorum sensing in microbes. The compounds are AI-2 analogs and as such have structures similar to 4,5-dihydroxy-2,3-pentanedione that can act as agonists/antagonists of quorum sensing. The compounds are useful for modulating quorum sensing in bacteria and can be used in methods for prophylaxis or therapy of bacterial infections and for reduction of biofilms.
Claims8
A compound having the following structure:
- wherein R and R3 are each are each independently a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group, ii) R is a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group and R3 is a H or keto group, or iii) R3 is a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group and R is a H or keto group,
- A is selected from the group consisting of:
- S, NH, CH2, O, CZ2, and CHZ, where Z is a halogen,
- Y is selected from the group consisting of:
- CH2, CZ2, and C═O, where Z is a halogen,
- X is selected from the group consisting of:
- CH, C—CH3, and N,
- R1 is selected from the group consisting of:
- H, C1 to C16 substituted or unsubstituted branched alkyl group, C1 to C16 substituted or unsubstituted linear alkyl group, C1 to C16 heterocyclic ring, and C3 to C8 carbocyclic ring, and
- R2 is selected from the group of:
- H and CH3,
- wherein, optionally, taken together R1—X—R2 form a C3 to C8 carbocyclic ring or heterocyclic ring, and the ring is, optionally, substituted,
- wherein, optionally, X is CH, R1 is CRxRy, and Rx is H or C1 to C16 substituted or unsubstituted linear alkyl group, Ry is H or C1 to C16 substituted or unsubstituted linear alkyl group, and the bond between R1 and X is a double bond,
- wherein, optionally, X is CH, and R1 and X are each bonded to a single O to form an epoxide, wherein, optionally, A is a N, and taken together A and R form a 1,2,5-thiadiazolidin-3-one 1,1-dioxide,
- wherein if X is CH, then R1 and R2 are not H, and
- wherein if X is CH, then R1 is not H and R2 is not CH3.
13 more elements
A method for modulating quorum sensing (QS) in a population of bacteria comprising contacting the population of bacteria with a composition comprising a compound having the following structure (I):
- wherein i) R and R3 are each are each independently a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group, ii) R is a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group and R3 is a H or keto group, or iii) R3 is a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group and R is a H or keto group,
- A is selected from the group consisting of:
- S, NH, CH2, O, CZ2, and CHZ, where Z is a halogen;
- Y is selected from the group consisting of:
- CH2, CZ2, and C═O, where Z is a halogen;
- X is selected from the group consisting of:
- CH, C—CH3, and N;
- R1 is selected from the group consisting of:
- H, C1 to C16 substituted or unsubstituted branched alkyl group, C1 to C16 substituted or unsubstituted linear alkyl group, C1 to C16 heterocyclic ring, and C3 to C8 carbocyclic ring, and
- R2 is selected from the group of:
- H and CH3,
- wherein, optionally, taken together R1—X—R2 form a C3 to C8 carbocyclic ring or heterocyclic ring, and the ring is, optionally, substituted,
- wherein, optionally, X is CH, R1 is CRxRy, and Rx is H or C1 to C16 substituted or unsubstituted linear alkyl group, Ry is H or C1 to C16 substituted or unsubstituted linear alkyl group, and the bond between R1 and X is a double bond,
- wherein, optionally, X is CH, and R1 and X are each bonded to a single O to form an epoxide,
- wherein, optionally, A is a N, and taken together A and R form a 1,2,5-thiadiazolidin-3-one 1,1-dioxide, and
- wherein if X is CH, then R1 and R2 are not H, and
- wherein if X is CH, then R1 is not H and R2 is not CH3.
14 more elements
A pharmaceutical preparation comprising a composition a compound having the following structure (I):
- wherein i) R and R3 are each are each independently a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group, ii) R is a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group and R3 is a H or keto group, or iii) R3 is a phosphonate group, sulfonate group, sulfoxide group, or carboxylate group and R is a H or keto group,
- A is selected from the group consisting of:
- S, NH, CH2, O, CZ2, and CHZ, where Z is a halogen;
- Y is selected from the group consisting of:
- CH2, CZ2, and C═O, where Z is a halogen;
- X is selected from the group consisting of:
- CH, C—CH3, and N;
- R1 is selected from the group consisting of:
- H, C1 to C16 substituted or unsubstituted branched alkyl group, C1 to C16 substituted or unsubstituted linear alkyl group, C1 to C16 heterocyclic ring, and C3 to C8 carbocyclic ring, and
- R2 is selected from the group of:
- H and CH3,
- wherein, optionally, taken together R1—X—R2 form a C3 to C8 carbocyclic ring or heterocyclic ring, and the ring is, optionally, substituted,
- wherein, optionally, X is CH, R1 is CRxRy, and Rx is H or C1 to C16 substituted or unsubstituted linear alkyl group, Ry is H or C1 to C16 substituted or unsubstituted linear alkyl group, and the bond between R1 and X is a double bond,
- wherein, optionally, X is CH, and R1 and X are each bonded to a single O to form an epoxide,
- wherein, optionally, A is a N, and taken together A and R form a 1,2,5-thiadiazolidin-3-one 1,1-dioxide, and
- wherein if X is CH, then R1 and R2 are not H, and
- wherein if X is CH, then R1 is not H and R2 is not CH3.
14 more elements
Dependencies are inferred from the claim text.