Structure-activity relationships of salicylic acid and its analogs in the inhibitory action on ^β-lactamase

AimNineteen compounds related to salicylic acid were evaluated for their in vitro activity of inhibiting ^β-lactamase isolated from a resistant strain of ^{Pseudomonas aeruginosa}, and their structure-activity relationships were examined. MethodsNitrocefin method was used. ResultsThe 50% inhibitory concentration (IC₅₀) of salicylic acid inhibiting ^β-lactamase was 22 mmol·L^-1; four analogs had IC₅₀ lower than that of salicylic acid; fifteen analogs had IC₅₀ higher than that of salicylic acid. ConclusionExamination of the structure-activity relationships of the compounds revealed that carboxyl group and adjoining hydroxyl group were active group, and replacement of adjoining hydroxyl by carboxyl increased activity nearly 4-fold. Moreover, addition of a sulfonic group at C-5 and nitro group at C-3,5 of benzenoic ring of salicylic acid resulted in a 2-fold to 3-fold increase in activity, addition of a amino group at C-5 of benzenoic ring of salicylic acid decreased activity, add addition of -Cl or -F at C-2,4 position of benzenoic ring of benzoic acid did not show activity.