[Structure-activity relationships of salicylic acid and its analogs in the inhibitory action on beta-lactamase].
OBJECTIVE
Nineteen 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.


METHODS
Nitrocefin method was used.


RESULTS
The 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.


CONCLUSIONS
Examination 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.
Yang
Zai-chang
ZC
Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang.
Yang
Xiao-sheng
XS
Wang
Bo-chu
BC
Sun
Qian-yun
QY
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism; D020128:Inhibitory Concentration 50; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000302:isolation & purification / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D012459:Salicylates; D001618:beta-Lactamases; C021720:nitrocefin