Autoinducer compounds
Autoinducer compounds which enhance gene expression in a wide variety of microorganisms, therapeutic compositions and therapeutic methods wherein gene expression within microorganisms is regulated are disclosed.
1 . A compound of the following formula:
wherein R 1 -R 2 , are selected from the group consisting of H, C 1 -C 4 alkyl group, OH, NH 2 , SH and a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine;
R 22 and R 23 are selected from H, S, O, and N—Y,
Y is selected from H, C 1 -C 4 alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine,
R 24 -R 28 is H or a halogen, and
X 1 and X 2 are selected from O, S, NH, H 2 , H plus OH or NH 2 , or any combination of H plus one halogen or two halogens when one or more R groups is substituted, and at least one of R 1 -R 21 is halogen, or the alkylene chain of the molecule contains a sulfur in the chain.
2 . The compound of claim 1 , wherein R 24 through R 28 are a H or halogen, and R 22 -R 23 are a H.
3 . The compound of claim 2 , wherein one or more carbons forming the backbone of the molecule are substituted with S or S-substituted moieties.
4 . The compound of claim 2 , wherein the carbonyl group at X 1 and/or X 2 is substituted with H 2 , H plus a halogen or two halogens.
5 . The compound of claim 1 , wherein R 22 is selected from H, S, O and N—Y, and R 23 is independently selected from S, O, and N—Y, wherein Y is selected from H, C 1 -C 4 alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine.
6 . The compound of claim 1 , wherein the alkylene side chain contains one or more double bonds or triple bonds between carbon atoms within the alkylene side chain.
7 . The compound of claim 1 , wherein X 1 -X 2 is selected from H 2 , H plus a halogen, two halogens, H plus OH or NH 2 , a double bonded O, NH, or S.
8 . The compound of claim 1 , which is an optically active isomer.
9 . A compound of the following formula:
wherein R 1 -R 7 are selected from the group consisting of H, C 1 -C 4 alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine;
R 22 and R 23 are selected from H, S, O, and N—Y,
Y is selected from H, C 1 -C 4 alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine,
R 24 —R 29 is H or a halogen, and
X is selected from O, S, NH, H 2 , H plus OH or NH 2 , or any combination of H plus one halogen or two halogens when one or more R groups is substituted, and at least one of R 1 -R 7 is halogen, or the alkylene chain of the molecule contains a sulfur in the chain.
10 . The compound of claim 9 , wherein R 22 is selected from H, S, O and N—Y, and R 23 is independently selected from S, O, and N—Y, wherein Y is selected from H, C 1 -C 4 alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine.
11 . The compound of claim 9 , wherein the alkylene side chain contains one or more double bonds or triple bonds between carbon atoms within the alkylene side chain.
12 . The compound of claim 9 , wherein X is selected from H 2 , H plus a halogen, two halogens, H plus OH or NH 2 , a double bonded O, NH or S.
13 . The compound of claim 9 , which is an optically active isomer.
14 . The compound of claim 1 , which is selected from the group consisting of:
15 . The compound of claim 1 , which is selected from the group consisting of:
16 . A pharmaceutical composition comprising at least one compound of the following formulae:
wherein R 1 -R 2 , are selected from the group consisting of H, C 1 -C 4 alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine;
R 22 and R 23 are selected from H, S, O, and N—Y,
Y is selected from H, C 1 -C 4 alkyl group, OH, NH 2 , SH or a halogen, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine, and iodine,
R 24 -R 28 is H or a halogen, and
X, X 1 and X 2 are selected from O, S, NH, H 2 , H plus OH or NH 2 , or any combination of H plus one halogen or two halogens when one or more R groups is substituted, and at least one of R 1 -R 21 is halogen, or the alkylene chain of the molecule contains a sulfur in the chain,
and a pharmaceutically acceptable carrier.
17 . The composition of claim 16 , wherein the compound is present in an amount effective to affect the ability of a microorganism to initially infect or further infect an organism.
18 . The composition of claim 16 , further comprising an antimicrobial, antibacterial or antifungal agent.
19 . A growth medium for microorganisms comprising a compound of the formula as defined in claim 1 or 9 , at a concentration effective to stimulate or promote the metabolism, growth and/or recovery of the microorganisms.
20 . A method for regulating gene expression with a microorganism, which method comprises inserting a gene into a microorganism chosen for enhancement of gene expression by a compound of the formula as defined in claim 1 or 9 , capable of stimulating the activity of a selected protein and incubating the microorganism with the compound.
21 . A method for regulating gene expression comprising adding a compound of the formula as defined in claim 1 or 9 , to a microorganism culture to cause expression of a selected gene that would not otherwise be expressed.
22 . A method of inhibiting the infectivity of a selected microorganism, comprising contacting the selected microorganism with a compound of the formula as defined in claim 1 or 9 .
23 . A compound according to claim 1 wherein R 1 -R 21 is CH 3 .
24 . A compound according to claim 9 wherein R 1 -R 7 is CH 3 .
25 . A composition according to claim 16 wherein R 1 -R 21 is CH 3 .
26 . A compound according to claim 1 which is an optical isomer.
27 . A compound according to claim 9 which is an optical isomer.
28 . A composition of claim 16 wherein the compound is an optical isomer.