Abstract
Sulfate-reducing bacteria (SRB) are most likely involved in both the initiation and maintenance of inflammatory bowel disease (IBD); unfortunately present antibacterial chemotherapeutics used in the treatment of IBD have been ineffective. Thus, the antimicrobial activity of salicylamide derivatives against two different genera of intestinal SRB, Desulfovibrio and Desulfomicrobium, was investigated. Six 2-(phenylcarbamoyl)phenyl N-[(benzyloxy)carbonyl]alkanoates and three 2-hydroxy-N-[(2S)-1-oxo-1-(phenylamino)alkan-2-yl]benzamides showed MIC values in the range from 0.22 to 0.35μM against Desulfovibrio piger Vib-7 and in the range from 0.27 to 8.52μM against Desulfomicrobium sp. Rod-9, while MIC values of ciprofloxacin were 41.2μM and 39.3μM. The highest potency against the two strains was observed for 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (MIC 0.22μM and 0.27μM). 4-Chloro-2-[(4-nitrophenyl)carbamoyl]phenyl (2S)-2-{[(benzyloxy)carbonyl]amino}-3-methylbutanoate showed high activity against D. piger Vib-7 (MIC=0.26μM), while 4-chloro-2-[(4-methylphenyl)carbamoyl]phenyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-2-yl)propanoate expressed high activity against Desulfomicrobium sp. Rod-9 (MIC=0.31μM). Structure–activity relationships are discussed.
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