Autoinducer compounds
View Patent ↗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 21 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,
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
wherein the alkylene chain of the molecule contains a nitrogen in the chain, or the alkylene chain of the molecule contains one or more double bonds or triple bonds between the carbon atoms within the chain, or the homoserine lactone portion of the molecule contains a sulfur in the ring.
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 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.
7. The compound of claim 1 , which is an optically active isomer.
8. 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 28 is H or a halogen,
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; and
wherein the alkylene chain of the molecule contains a nitrogen in the chain, or the alkylene chain of the molecule contains one or more double bonds or triple bonds between the carbon atoms within the chain, or the homoserine lactone portion of the molecule contains a sulfur in the ring.
9. The compound of claim 8 , 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.
10. The compound of claim 8 , 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.
11. The compound of claim 8 , which is an optically active isomer.
12. A pharmaceutical composition comprising at least one compound of the following formulae:
wherein R 1 –R 21 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,
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
wherein the alkylene chain of the molecule contains a nitrogen in the chain, or the alkylene chain of the molecule contains one or more double bonds or triple bonds between the carbon atoms within the chain, or the homoserine lactone portion of the molecule contains a sulfur in the ring.
and a pharmaceutically acceptable carrier.
13. The composition of claim 12 , wherein the compound is present in an amount effective to affect the ability of a microorganism to initially infect or further infect an organism.
14. The composition of claim 12 , further comprising an antimicrobial, antibacterial or antifungal agent.
15. A growth medium for microorganisms comprising a compound of the formula as defined in claim 1 or 8 , at a concentration effective to stimulate or promote the metabolism, growth and/or recovery of the microorganisms.
16. 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 8 , capable of stimulating the activity of a selected protein and incubating the microorganism with the compound.
17. A method for regulating gene expression comprising adding a compound of the formula as defined in claim 1 or 8 , to a microorganism culture to cause expression of a selected gene that would not otherwise be expressed.
18. 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 8 .
19. A compound according to claim 1 wherein R 1 –R21 is CH 3 .
20. A compound according to claim 8 wherein R 1 –R 7 is CH 3 .
21. A composition according to claim 12 wherein R 1 –R 21 is CH 3 .
22. A compound according to claim 1 which is an optical isomer.
23. A compound according to claim 8 which is an optical isomer.
24. A composition of claim 12 wherein the compound is an optical isomer.