Structure-activity relationships of salicylic acid and its analogs in the inhibitory action on beta-lactamase.
- Author:
Zai-chang YANG
1
;
Xiao-sheng YANG
;
Bo-chu WANG
;
Qian-yun SUN
Author Information
- Publication Type:Journal Article
- MeSH: Anti-Bacterial Agents; chemical synthesis; chemistry; pharmacology; Cephalosporins; metabolism; Inhibitory Concentration 50; Pseudomonas aeruginosa; enzymology; Salicylates; chemical synthesis; chemistry; pharmacology; Structure-Activity Relationship; beta-Lactamases; isolation & purification; metabolism
- From: Acta Pharmaceutica Sinica 2006;41(3):230-232
- CountryChina
- Language:Chinese
-
Abstract:
AIMNineteen compounds related to salicylic acid were evaluated for their in vitro activity of inhibiting beta-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 beta-lactamase was 22 mmol x 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.
