title: Antistaphylococcal activity of novel salicylanilide derivatives.
abstract: This study examined the antibacterial properties of nineteen benzoxazole, isoniazid, ethionamide and salicylanilide derivatives against Staphylococcus aureus (S. aureus). It was found that three salicylanilide-derived compounds demonstrated antistaphylococcal activity: 5-Chloro-2-hydroxy-N-(4-(trifluoromethyl)phenyl)benzamide (5-Cl-4'-CF3- SAL), 4-chloro-2-(3-chlorophenylcarbamyoyl)phenyl)-2-(benzyloxycarbonylamino)propanoate (AIM31) and 4-chloro-2- (4-(trifluoromethyl)phenylcarbamoyl)phenyl acetate (AIM33). Investigation of the chemical structures of these three compounds and comparison with a non-inhibitory salicylanilide compound (i.e. 5,3'-diCl-SAL) illustrated that different combinations of chemical groups at defined positions on the salicylanilide core structure had a marked influence on antistaphylococcal activity. The most effective compound was AIM33 which inhibited staphylococcal growth and displayed an initial MIC value of 3.12 μg ml(-1) and subsequent investigation revealed that an MIC as low as of 0.5 μg ml(-1) was achievable. In this case, the dual presence of a trifluoromethyl group and an acetylated phenolic hydroxyl to the salicylanilide core structure led to greatly enhanced activity.
authors.affiliation: Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland.
authors.forename: Annmarie
authors.initials: A
authors.lastname: Mollaghan
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinsova
authors.forename: Ales
authors.initials: A
authors.lastname: Imramovsky
authors.forename: Lesley
authors.initials: L
authors.lastname: Cotter
authors.forename: Brigid
authors.initials: B
authors.lastname: Lucey
authors.forename: Jim
authors.initials: J
authors.lastname: O'Mahony
authors.forename: Aisling
authors.initials: A
authors.lastname: Costelloe
authors.forename: Aidan
authors.initials: A
authors.lastname: Coffey
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D012458:Salicylanilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D012458:Salicylanilides