A small library of 4-(alkylamino)-3-nitrocoumarin derivatives with potent antimicrobial activity against gastrointestinal pathogens

Abstract

Due to the confirmed antimicrobial activity of both natural and synthetic coumarin derivatives, the present study was envisaged to provide further insight into the antimicrobial potential of coumarins through the screening of a designed library of nine 4-(alkylamino)-3-nitrocoumarins against a panel of 24 laboratory strains and resistant (isolates) bacterial and fungal pathogens. All compounds showed some degree of strain-selective activity that in some cases was very pronounced, reaching the value of 0.04 nmol mL-1 (i.e., 12 ng mL-1) for the minimal inhibitory concentration against Candida albicans. The observed activities were higher against Gram-negative strains, among which the most susceptible strain, among both ATCC strains and clinical isolates, was Salmonella enterica subsp. enterica serovar Enteritidis. These results indicate to a high potential of these coumarins as antimicrobials for the treatment of gastrointestinal and other infections caused by highly resistant microbial strains. Finally, a multivariate statistical analysis of the herein obtained and previous results on the antimicrobial activity of related selected coumarins was performed to allow an easier structure-activity discussion.