US2008027115A1PendingUtilityA1
Combinatorial libraries of autoinducer analogs, autoinducer agonists and antagonists, and methods of use thereof
Assignee: UNIV NEW YORK STATE RES FOUNDPriority: Aug 15, 2002Filed: Aug 6, 2007Published: Jan 31, 2008
Est. expiryAug 15, 2022(expired)· nominal 20-yr term from priority
C07D 285/13C07C 237/42C07D 213/56Y02P20/582C07C 2601/08A61P 43/00A61K 31/435C07C 235/74C07D 217/26C07D 309/10A61P 31/00A61K 31/166A61K 31/44C07D 319/06A61P 31/04C07C 2601/14C07D 231/56
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Claims
Abstract
The present invention relates to solid phase or solution phase combinatorial libraries of autoinducer analogs. The present invention also relates to autoinducer agonists and antagonists. In addition, the present invention relates to methods for identifying autoinducer agonists and antagonists, as well as methods for regulating the activity of an autoinducer receptor, regulating biofilm formation, regulating growth or virulence of an organism in a subject, inhibiting the quorum sensing mechanism of an organism, and treating an infection in a subject caused by an organism possessing a quorum sensing mechanism which use the autoinducer analogs of the present invention.
Claims
exact text as granted — not AI-modified1 . A combinatorial library of autoinducer analogs comprising two or more different autoinducer analogs of the structure
wherein X 1 is independently selected from the group consisting of H and OH, X 2 is independently selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, ● is a solid support, and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, ● is a solid support, and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and ● is a solid support; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and ● is a solid support, and wherein R is selected from the group consisting of C m H 2m , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH and X 5 is H, or X 4 is H and X 5 is OH.
2 . The combinatorial library according to claim 1 , wherein the library includes at least one compound selected from the group consisting of
3 . The combinatorial library according to claim 1 , wherein at least one member of the library is an autoinducer agonist or an autoinducer antagonist.
4 . The combinatorial library according to claim 3 , wherein the autoinducer is produced by an organism selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
5 . The combinatorial library according to claim 4 , wherein at least one member of the library is a Pseudomonas aeruginosa autoinducer agonist or autoinducer antagonist.
6 . The combinatorial library according to claim 5 , wherein Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
7 . The combinatorial library according to claim 6 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
8 . The combinatorial library according to claim 1 , wherein the solid support is 3,4-dihydro-2H-pyran-2-ylmethoxymethyl polystyrene.
9 . A combinatorial library of autoinducer analogs comprising two or more different autoinducer analogs of the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH.
10 . The combinatorial library according to claim 9 , wherein the library includes at least one compound selected from the group consisting of
11 . The combinatorial library according to claim 9 , wherein at least one member of the library is an autoinducer agonist or an autoinducer antagonist.
12 . The combinatorial library according to claim 9 , wherein the autoinducer is produced by an organism selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
13 . The combinatorial library according to claim 12 , wherein at least one member of the library is a Pseudomonas aeruginosa autoinducer agonist or autoinducer antagonist.
14 . The combinatorial library according to claim 13 , wherein Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
15 . The combinatorial library according to claim 14 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
16 . An autoinducer agonist or antagonist having the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH.
17 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer agonist having the structure
18 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer agonist having the structure
19 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer antagonist having the structure
20 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer antagonist having the structure
21 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer antagonist having the structure
22 . The autoinducer agonist antagonist according to claim 16 comprising an autoinducer antagonist having the structure
23 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer antagonist having the structure
24 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer antagonist having the structure
25 . The autoinducer agonist or antagonist according to claim 16 comprising an autoinducer antagonist having the structure
26 . The autoinducer agonist or antagonist according to claim 16 , wherein the autoinducer is produced by an organism selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
27 . The autoinducer agonist or antagonist according to claim 26 , wherein the autoinducer is a Pseudomonas aeruginosa autoinducer.
28 . The autoinducer agonist or antagonist according to claim 27 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
29 . The autoinducer agonist or antagonist according to claim 28 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
30 . A method of identifying an autoinducer agonist comprising:
providing an autoinducer analog having the structure wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14, wherein p is 1 to 14, and wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH.; contacting the autoinducer analog with an autoinducer receptor; and measuring activity of the autoinducer receptor in the presence of the autoinducer analog.
31 . The method according to claim 30 , wherein the autoinducer analog is an autoinducer agonist.
32 . The method according to claim 30 , wherein the autoinducer receptor is present in an organism is selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
33 . The method according to claim 32 , wherein the autoinducer receptor is LasR, LasI, RhlR, or RhlI of Pseudomonas aeruginosa.
34 . A method of identifying an autoinducer antagonist comprising:
providing an autoinducer analog having the structure wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14, wherein p is 1 to 14, and wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH; contacting the autoinducer analog with an autoinducer receptor and an autoinducer, whereby competition between the autoinducer analog and the autoinducer for the autoinducer receptor is allowed to occur; measuring activity of the receptor in the presence of the autoinducer analog and autoinducer; and comparing the measured activity with an activity of the receptor in the presence of only the autoinducer.
35 . The method according to claim 34 , wherein the autoinducer analog is an autoinducer antagonist.
36 . The method according to claim 34 , wherein the autoinducer receptor is present in an organism is selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
37 . The method according to claim 36 wherein the autoinducer receptor is LasR, LasI, RhlR, or RhlI of Pseudomonas aeruginosa.
38 . The method according to claim 34 , wherein the autoinducer is produced by an organism selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
39 . The method according to claim 38 , wherein the autoinducer is a Pseudomonas aeruginosa autoinducer.
40 . The method according to claim 39 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
41 . The method according to claim 40 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
42 . A composition comprising an autoinducer analog having the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH and a pharmaceutical carrier or diluent.
43 . The composition according to claim 42 , wherein the autoinducer analog is an autoinducer antagonist.
44 . The composition according to claim 43 , wherein the autoinducer is produced by an organism is selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
45 . The composition according to claim 44 , wherein the autoinducer analog is a Pseudomonas aeruginosa autoinducer antagonist.
46 . The composition according to claim 45 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
47 . The composition according to claim 46 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
48 . The composition according to claim 42 further comprising an antibiotic.
49 . The composition according to claim 48 , wherein the antibiotic is selected from the group consisting of carbapenems and aminoglycosides.
50 . A method for regulating the activity of an autoinducer receptor comprising contacting an autoinducer receptor with an autoinducer analog having the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH, whereby activity of the autoinducer receptor is regulated.
51 . The method according to claim 50 , wherein the autoinducer analog is an autoinducer agonist or an autoinducer antagonist.
52 . The method according to claim 51 , wherein the autoinducer analog is a Pseudomonas aeruginosa autoinducer agonist or autoinducer antagonist.
53 . The method according to claim 52 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
54 . The method according to claim 53 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
55 . The method according to claim 50 , wherein the autoinducer receptor is found on a bacterial cell.
56 . The method according to claim 55 , wherein the bacterial cell is within a host organism.
57 . The method according to claim 50 , wherein the autoinducer receptor is present in an organism is selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
58 . The method according to claim 57 , wherein the autoinducer receptor is LasR, LasI, RhlR, or RhlI of Pseudomonas aeruginosa.
59 . A method of regulating biofilm formation comprising contacting a cell of an organism with an autoinducer analog having the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH, whereby biofilm formation on the cell is regulated.
60 . The method according to claim 59 , wherein biofilm formation is inhibited.
61 . The method according to claim 59 , wherein biofilm architecture is modified by contact with the autoinducer analog.
62 . The method according to claim 59 , wherein the autoinducer analog is an autoinducer antagonist.
63 . The method according to claim 62 , wherein the autoinducer analog is a Pseudomonas aeruginosa autoinducer antagonist.
64 . The method according to claim 63 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
65 . The method according to claim 64 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
66 . A method for controlling the growth or virulence of an organism in a subject comprising contacting a cell of an with an autoinducer analog having the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH, whereby growth or virulence of the organism in a subject is regulated.
67 . The method according to claim 66 , wherein the autoinducer analog is an autoinducer agonist and growth of the organism is enhanced.
68 . The method according to claim 66 , wherein the autoinducer analog is an autoinducer antagonist and growth of the organism is inhibited.
69 . The method according to claim 66 , wherein the autoinducer analog is an autoinducer antagonist and virulence is inhibited.
70 . The method according to claim 66 , wherein the autoinducer analog is a Pseudomonas aeruginosa autoinducer agonist or antagonist.
71 . The method according to claim 70 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
72 . The method according to claim 71 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
73 . A method of inhibiting a quorum sensing mechanism in an organism comprising contacting a cell of an organism possessing a quorum sensing mechanism with an autoinducer analog having the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH, whereby the quorum sensing mechanism of the cell is inhibited.
74 . The method according to claim 73 , wherein the autoinducer analog is an autoinducer antagonist.
75 . The method according to claim 74 , wherein the autoinducer analog is a Pseudomonas aeruginosa autoinducer antagonist.
76 . The method according to claim 75 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
77 . The method according to claim 76 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
78 . The method according to claim 73 , wherein the organism is selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
79 . A method of treating an infection in a subject caused by a organism possessing a quorum sensing mechanism comprising administering to the subject an effective amount of a composition comprising an autoinducer analog having the structure
wherein X 1 is selected from the group consisting of H and OH, X 2 is selected from the group consisting of H and OH, X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 3 is independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl and n is 0 to 4; or
wherein X 1 , X 2 , and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 1 , X 2 , and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl; or
wherein X 2 and X 3 are independently selected from the group consisting of H, OH, SH, OR 1 , SR 1 , NH 2 , NHR 1 , NR 1 R 2 , COOR 1 , alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, acyl group, carbonyl, cyano, nitro, halogen, and, adjacent X 2 and X 3 substituents combined, a cycloalkyl of 3 to 8 carbon atoms, a heterocycloalkyl of 3 to 8 members comprising carbon atoms and from 1 to 6 heteroatoms selected from the group consisting of N, S, and O, and an aryl or heteroaryl ring having 3 to 8 members, wherein R 1 and R 2 are selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, aryl, heteroaryl, carbonyl, and sulfonyl, and wherein R is selected from the group consisting of C m H 2m+1 , wherein m is 1 to 14,
wherein p is 1 to 14, and
wherein q is 1 to 14, X 4 is OH, NH 2 , or SH and X 5 is H, or X 4 is H and X 5 is OH, NH 2 , or SH and a pharmaceutical carrier or diluent.
80 . The method according to claim 79 , wherein the autoinducer analog is an autoinducer antagonist.
81 . The method according to claim 80 , wherein the autoinducer analog is a Pseudomonas aeruginosa autoinducer antagonist.
82 . The method according to claim 81 , wherein the Pseudomonas aeruginosa autoinducer is selected from the group consisting of N-(3-oxododecanoyl)-L-homoserine lactone, N-butyloyl-L-homoserine lactone, and 2-heptyl-3-hydroxy-4-quinolone.
83 . The method according to claim 82 , wherein the Pseudomonas aeruginosa autoinducer is N-(3-oxododecanoyl)-L-homoserine lactone.
84 . The method according to claim 79 , wherein the organism is selected from the group consisting of Pseudomonas aeruginosa, Aeromonas hydrophilia, Aeromonas salmonicida, Yersinia pseudotuberculosis, Helicobacter pylori, Agrobacterium tumefaciens, Vibrio fischeri, Vibrio harveyi, Erwinia carotovora, Rhizobium leguminosarum, Rhodobacter sphaeroides , and Escherichia coli.
85 . The method according to claim 79 , wherein the subject is a mammal.
86 . The method according to claim 85 , wherein the mammal is a human.
87 . The method according to claim 79 , wherein the composition further comprises an antibiotic.
88 . The method according to claim 87 , wherein the antibiotic is selected from the group consisting of carbapenems and aminoglycosides.Join the waitlist — get patent alerts
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