Modulation of pathogenicity
The present invention relates to the use of compounds of the general Formula (XIII): wherein A 7 is C═O, C═S, SO 2 , CH—OR 13 , C═NR 12 , or CH 2 —CHOR 13 ; A 8 is C(R 14 ) 2 , O, S, or NR 12 ; A 9 is C═O, C═S, SO 2 , CH—OR 13 , C═NR 12 , or CH 2 —CHOR 13 ; m is 0, or 1 q is 0, or 1 r is 0, or 1 R 12 is H, CH 3 , CH 2 —CH 3 , C 6 H 5 , OCH 3 , OCH 2 —CH 3 , OH, or SH; R 13 is H, CH 3 , or CH 2 —CH 3 ; R 14 is H, alkyl, alkoxy, OH, or SH;
1 . A compound of Formula (XIII):
or a pharmaceutically acceptable salt or physiologically acceptable derivative thereof wherein
A 7 independently is C═O, C═S, SO 2 , CH—OR 13 , C═NR 12 , or CH 2 —CHOR 13 ;
A 8 independently is C(R 14 ) 2 , O, S, or NR 12 ;
A 9 independently is C═O, C═S, SO 2 , CH—OR 13 , C═NR 12 , or CH 2 —CHOR' 3 ;
m is 0 or 1;
q is 1;
r is 1;
R 12 is independently H, CH 3 , CH 2 —CH 3 , C 6 H 5 , OCH 3 , OCH 2 —CH 3 , OH, or SH;
R 13 is independently H, CH 3 , or CH 2 —CH 3 ;
R 14 is independently H, alkyl, alkoxy, OH, or SH;
A 5 is an optionally substituted C 3 -C 16 -alkyl group by one or more substituents R 3 ,
A 6 is an optionally substituted thiazole group, which can optionally be substituted by one or more substituents R 8 , R 8 , or R 9 ,
each of R 8 , R 8 —, R 9 independently is methyl, ethyl, t-butyl, CN, halogen, haloalkoxy, haloalkyl, OH, alkoxy, NR 4 R 5 , COOR 4 , COR 4 , or SR 4 ;
each R 3 independently is OR 4 , SR 4 , hydroxyalkyl, hydroxyalkylamino, cycloalkyl, halogen, haloalkyl, haloalkyloxy, NO 2 , CN, SO 2 NR 4 R 5 , CONR 4 R 5 , COR 4 , CO 2 R 4 , SO 2 R 4 , SO 3 R 4 , NR 4 R 5 , alkyl, aryl or heteroaryl;
R 4 is H, alkyl, cycloalkyl, aryl or heteroaryl; and
R 5 is H, O-alkyl, O-aryl, alkyl, heteroaryl or aryl.
2 . A pharmaceutical composition comprising a compound according to claim 1 .
3 . A method for the treatment of bacterial damage or disease which comprises administering to a patient or applying to an object in need thereof a suitable amount of a compound according to claim 1 .
4 . A method for regulating quorum sensing system of a microorganism comprising contacting the microorganism with a compound according to claim 1 .
5 . The method according to claim 4 , wherein the microorganism is a bacterium
6 . The method according to claim 4 , wherein the microorganism is a gram negative bacterium.
7 . The method according to claim 4 , wherein quorum sensing of the microorganism is inhibited.
8 . The method according to claim 3 , wherein the bacterial damage or disease is caused by Pseudomonas aeruginosa, Burkholderia cepacia, Aeromonas hydrophila, Chromobacterium violaceum, Escherichia coli, Yersinia enterocolitica, Y. pseudotuberculosis , or Serratia liquefaciens.
9 . The method according to claim 8 , wherein the damage or disease is in an immunocompromized or cystic fibrosis patient.
10 . A method for treating biofilm or inhibiting of the formation of biofilm on an object, wherein the biofilm comprises at least a bacterium having a quorum sensing system, the method comprising application of a compound of claim 1 .
11 . The method according to claim 10 , wherein the object is medical instrument, a medical device, a preparation of disinfectant, a preparation of cleaning solution, a personal hygiene article, a toiletry, a cosmetic preparation, a ship hull, an industrial system, or an environmental system.
12 . The method according to claim 11 , wherein the industrial system or environmental system is selected from the group consisting of a food processing system, a oil recovery system, a paper manufacturing plant, a water treatment plant, a water distribution system, and a refrigeration system.
13 . The method according to claim 10 , wherein a plant disease is treated or damage to the plants caused by an infection by the microorganism is prevented or alleviated.