Antimicrobial effect of salicylamide derivatives against intestinal sulfate-reducing bacteria

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 0.35 mu M against Desulfovibrio piger Vib-7 and in the range from 0.27 to 8.52 mu M against Desulfomicrobium sp. Rod-9, while MIC values of ciprofloxacin were 41.2 mu M and 39.3 mu M. 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 0.22 mu M and 0.27 mu M). 4-Chloro-2-[(4-nitrophenyl) carbamoyl]phenyl (2S)-2-{[(benzyloxy)carbonyl]amino}-3-methylbutanoate showed high activity against D. piger Vib-7 (MIC = 0.26 mu M), 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 = 0.31 mu M). Structure-activity relationships are discussed. (C) 2016 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Sp. z o.o. All rights reserved.