Anti-microbial agents derived from methionine sulfoximine analogues
OwnerGunther Harth, Owen Griffith +1inventors
InventorsGunther Harth, Owen Griffith, Marcus Horwitz
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Abstract
Novel antimicrobial compositions containing analogues of L-methionine-SR-sulfoximine (MSO) that are effective in treating intracellular pathogen infections are provided. Specifically, the compositions provided are MSO analogues having superior antimicrobial activity with significantly less toxicity as compared to MSO. These MSO analogues are suitable for use in treating infection in animals including primates, cows, pigs, horses, rabbits, mice, rats, cats, and dogs. Moreover, the MSO analogues are ideally suited for treating infections caused by the genus Mycobacterium. Additionally, methods for using the novel MSO analogues are also provided.
Claims14
An anti-mycobacterial composition comprising a mycobacterial glutamine synthetase (MbGS) inhibitor of Formula 1:
- wherein:
- R1=branched and straight-chain alkyl groups of 1 to 8 carbons, and
- R2=tetrahedral group selected from the group consiting of:
- wherein said anti-mycobacterial composition effectively inhibits MbGS but does not substantially inhibit mammalian glutamine synthetase (MGS) in vivo.
An anti-mycobacterial composition comprising alpha-methyl-D,L-methionine-SR-sulfoxamine (α-Me-MSO) or alpha-ethyl-D,L-methionine-SR-sulfoxamine (α-Et-MSO) wherein said anti-mycobacterial composition effectively inhibits MbGS but does not substantially inhibit mammalian glutamine synthetase (MGS) in vivo.
An anti-mycobacterial composition comprising alpha-methyl-L-methionine-S-sulfoxamine (α-Me-MSO) or alpha-ethyl-L-methionine-S-sulfoxamine (α-Et-MSO) wherein said anti-mycobacterial composition effectively inhibits MbGS but does not substantially inhibit mammalian glutamine synthetase (MGS) in vivo.
A method for treating, palliating or inhibiting mycobacterial infections in a mammal comprising:
- administering to a mammal having a mycobacterial infection an anti-microbial effective amount of an anti-mycobacterial composition comprising gamma-substituted alpha-amino-alpha-alkyl-butyrates that effectively inhibit mycobacterial glutamine synthetase (MbGS), but do not substantially interfere with mammalian glutamine synthetase (MGS) in vivo such that said mycobacterial infection is treated, palliated or inhibited.
A method for treating, palliating or inhibiting mycobacterial infections in a mammal comprising:
- administering to a mammal having a mycobacterial infection an anti-microbial effective amount of an anti-mycobacterial composition comprising alpha-methyl-L-methionine-S-sulfoxamine (α-Me-MSO) or alpha-ethyl-L-methionine-S-sulfoxamine (α-Et-MSO) wherein said anti-mycobacterial composition effectively inhibits MbGS but does not substantially inhibit mammalian glutamine synthetase (MGS) in vivo.
A method for treating, palliating or inhibiting mycobacterial infections in a mammal comprising:
- co-administrating and anti-mycobacterial effective amount of L-methionine-SR-sulfoximine (MSO) and ascorbic acid.
Dependencies are inferred from the claim text.