Antimicrobial compounds

Abstract

The present invention relates to a compound of formula (I) AA-AA-AA-R 1 -R 2 (I) wherein, in any order, 2 of said AA (amino acid) moieties are cationic amino acids and 1 of said AA is an amino acid with a lipophilic R group, the R group having 14-27 non-hydrogen atoms; R 1 is a N atom, which may be substituted by a branched or unbranched C 1 -C 10 alkyl or aryl group, which group may incorporate up to 2 heteroatoms selected from N, O and S; and R 2 is an aliphatic moiety having 2-20 non-hydrogen atoms, said moiety being linear, branched or cyclic. The invention further relates to formulations containing these compounds, solid supports having these compounds attached thereto, the use of these compounds in therapy, particularly as antimicrobial, anti-tumour or anti-biofilm agents and non-therapeutic uses of these compounds, particularly their use in inhibiting biofilm formation or removing a biofilm.

1 . A compound of formula (I)
   AA-AA-AA-R 1 -R 2   (I)
   wherein, in any order, 2 of said AA (amino acid) moieties are cationic amino acids and 1 of said AA is an amino acid with a lipophilic R group, the R group having 14-27 non-hydrogen atoms;
 R 1  is a N atom, which may be substituted by a branched or unbranched C 1 -C 10  alkyl or aryl group, which group may incorporate up to 2 heteroatoms selected from N, O and S; and 
 R 2  is an aliphatic moiety having 2-20 non-hydrogen atoms, said moiety being linear, branched or cyclic. 
   
     
     
         2 . A compound of formula (I) as claimed in  claim 1 , wherein said compound is a peptide. 
     
     
         3 . A compound of formula (I) as claimed in  claim 1  or  claim 2 , wherein said cationic amino acids are lysine and/or arginine. 
     
     
         4 . A compound of formula (I) as claimed in any one of the preceding claims, wherein the lipohilic R group contains 2 or more cyclic groups which may be fused or connected. 
     
     
         5 . A compound of formula (I) as claimed in any one of the preceding claims, wherein R 1  is unsubstituted. 
     
     
         6 . A compound of formula (I) as claimed in any one of the preceding claims, wherein R 2  comprises 3 to 6 non-hydrogen atoms. 
     
     
         7 . A compound of formula (I) as claimed in any one of the preceding claims, wherein the non-hydrogen atoms of R 2  are carbon atoms. 
     
     
         8 . A compound of formula (I) as claimed in any one of the preceding claims, wherein R 2  is a linear or branched alkyl group. 
     
     
         9 . A compound of formula (I) as claimed in  claim 8 , wherein said alkyl group is selected from the group consisting of ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl and isomers thereof and hexyl and isomers thereof. 
     
     
         10 . A compound as claimed in  claim 1  being of formula (II)
   AA 1 -AA 2 -AA 1 -R 1 -R 2   (II)
 
 wherein: 
 AA 1  is a cationic amino acid; 
 AA 1  is an amino acid with a lipophilic R group, the R group having 14-27 non-hydrogen atoms; and 
 R 1  and R 2  are as defined in any preceding claim. 
 
     
     
         11 . A compound of formula (I) as claimed in any one of  claims 1  to  9  or a compound of formula (II) as claimed in  claim 10 , wherein the amino acid with a lipophilic R group, is selected from tributyl tryptophan (Tbt) or a biphenylalanine derivative selected from the group consisting of Phe (4-(2′-naphthyl)), Phe (4-(1′-naphthyl)), Phe(4-4′-n-butyl-phenyl), Phe (4-4′-biphenyl) and Phe(4-4′-t-butylphenyl). 
     
     
         12 . A compound as claimed in any one of the preceding claims, wherein —R 1 -R 2  together is selected from the group consisting of —NHCH(CH 3 ) 2 , —NH(CH 2 ) 5 CH 3 , —NH(CH 2 ) 3 CH 3 , —NH(CH 2 ) 2 CH 3 , —NHCH 2 CH(CH 3 ) 2 , —NHcyclohexyl and —NHcyclopentyl. 
     
     
         13 . A compound as claimed in  claim 12 , wherein —R 1 -R 2  together is —NHCH(CH 3 ) 2  or —NH(CH 2 ) 5 CH 3 . 
     
     
         14 . A compound as claimed in any one of the preceding claims for use in therapy. 
     
     
         15 . A compound as claimed in  claim 14  for use as an antimicrobial agent, an anti-biofilm agent or an anti-tumour agent. 
     
     
         16 . A compound as claimed in  claim 14  for use in treating or preventing a microbial infection, a biofilm-associated infection, a chronic wound or a tumour. 
     
     
         17 . A method of treating or preventing a microbial infection, a biofilm-associated infection, a chronic wound or a tumour in a subject, said method comprising the administration to the subject of a compound as claimed in any one of  claims 1  to  13 . 
     
     
         18 . A method of inhibiting biofilm formation or removing a biofilm, said method comprising contacting said biofilm with a compound as claimed in any one of  claims 1  to  13 . 
     
     
         19 . Use of a compound as claimed in any one of  claims 1  to  13  for inhibiting biofilm formation or removing a biofilm. 
     
     
         20 . A formulation comprising a compound as claimed in any one of  claims 1  to  13  in admixture with a suitable diluent, carrier or excipient. 
     
     
         21 . A formulation as claimed in  claim 20 , which is a pharmaceutical formulation. 
     
     
         22 . A solid support having attached thereto a compound as claimed in any one of  claims 1  to  13 .