Yang Zai-chang, Yang Xiao-sheng, Wang Bo-chu, Sun Qian-yun
Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang.
Yao Xue Xue Bao. 2006 Mar;41(3):230-2.
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.
Nitrocefin method was used.
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.
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.
评估19种与水杨酸相关的化合物对从铜绿假单胞菌耐药菌株中分离出的β-内酰胺酶的体外抑制活性，并研究其构效关系。
采用硝基头孢菌素法。
水杨酸抑制β-内酰胺酶的50%抑制浓度（IC50）为22 mmol·L⁻¹；4种类似物的IC50低于水杨酸；15种类似物的IC50高于水杨酸。
对这些化合物构效关系的研究表明，羧基和相邻羟基是活性基团，用羧基取代相邻羟基可使活性提高近4倍。此外，在水杨酸苯环的C-5位添加磺酸基和在C-3、5位添加硝基可使活性提高2至3倍，在水杨酸苯环的C-5位添加氨基会降低活性，在苯甲酸苯环的C-2、4位添加-Cl或-F则无活性。
