MODULATION OF BACTERIAL QUORUM SENSING WITH SYNTHETIC LIGANDS

摘要

The present invention provides compounds and methods for modulation of the quorum sensing of bacteria. In an embodiment, the compounds of the present invention are able to act as replacements for naturally occurring bacterial quorum sensing ligands in a ligand-protein binding system; that is, they imitate the effect of natural ligands and produce an agonistic effect. In another embodiment, the compounds of the present invention are able to act in a manner which disturbs or inhibits the naturally occurring ligand-protein binding system in quorum sensing bacteria; that is, they produce an antagonistic effect. The compounds of the present invention comprise N-acylated-homoserine lactones (AHLs) comprised of a wide range of acyl groups.

主权项

1. A method comprising the step of contacting a bacteria with an effective amount of a compound having the formula FX1: or a pharmaceutically acceptable salt or ester thereof, wherein m is 1, 2, 3, or 4; each R1, R2, and R3 is independently selected from the group consisting of —R, —COOR, —COR, —CON(R)2, —OCON(R)2, —N(R)2, —SR, —SO2R, —SOR, —OCOOR, —SO2N(R)2, and —OR; wherein R is selected from the group consisting of a hydrogen, a halogen, an amine group, a substituted or unsubstituted unbranched C1-C12 acyclic aliphatic group, a substituted or unsubstituted branched C1-C12 acyclic aliphatic group, a substituted or unsubstituted C3-C8cycloalkyl group, a substituted or unsubstituted C3-C8cycloalkenyl group, a fluorinated C1-C12 alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocycle, a substituted or unsubstituted C1-C12alkoxy group, a fluorinated C1-C12alkoxy group, a hydroxyl group, a nitrile group, an azide group, a nitro group, an acyl group, a thiol group, and a protecting group; additionally, R and R optionally form a ring; X is selected from the group consisting of S, O, NH, and CH2. Y is selected from the group consisting of: L is wherein one or more CH2 groups are optionally replaced by NH, O, S, a carbonyl (C═O), or a sulfonyl (S═O or O═S═O); two adjacent CH2 groups are optionally replaced by —CH═CH— or —C═C—; and wherein p is selected from the range of 0 to 15; Z is selected from the group consisting of:and n is 0 or 1; and
A is selected from the group consisting of an aryl group, a C5-C8 cycloalkyl group, a C5-C8 cycloalkenyl group, a heterocycle having a ring size of 5 to 8 atoms with 1, 2, or 3 hetereoatoms in the ring, an unbranched C1-C12 acyclic aliphatic group, or a branched C1-C12 acyclic aliphatic group, each of which is optionally substituted with one or more substituents selected from the group consisting of —R, —COOR, —COR, —CON(R)2, —OCON(R)2, —N(R)2, —SR, —SO2R, —SOR, —OCOOR, —SO2N(R)2, and —OR; wherein R is selected from the group consisting of a hydrogen, a halogen, an amine group, a substituted or unsubstituted unbranched C1-C12 acyclic aliphatic group, a substituted or unsubstituted branched C1-C12 acyclic aliphatic group, a substituted or unsubstituted C3-C8 cycloalkyl group, a substituted or unsubstituted C3-C8 cycloalkenyl group, a fluorinated C1-C12 alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocycle, a substituted or unsubstituted C1-C12 alkoxy group, a fluorinated C1-C12 alkoxy group, a hydroxyl group, a nitrile group, an azide group, a nitro group, an acyl group, a thiol group, and a protecting group; additionally, R and R optionally form a ring.