Design,Synthesis and Biological Evaluation of Sulfenimine Cephalosporin Analogues as β-Lactamase Inhibitors |
| |
| Authors: | ZHANG Kai DING Huaiwei SHI Ailong HUANG Qi SONG Hongrui FU Decai |
| |
| Affiliation: | 1. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
2. College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China |
| |
| Abstract: | A series of sulfenimine cephalosporin derivatives(6a-6t) was designed, synthesized and evaluated for their inhibitory activity against class A β-lactamase(TEM-1) derived from E. coli, and class C β-lactamase (cephalosporinase) derived from wild Bacillus subtilis in cell-free systems. Most of the tested compounds showed enhanced inhibitory activity against class C β-lactamase(cephalosporinase) compared with tazobactam. The most promising compounds 6c and 6o in combination with cefradine(IC50=1.80 and 1.59 μmol/L, respectively) were further investigated against a series of clinical isolated β-lactamase-producing bacterial strains. The results reveal that compounds 6c and 6o in combination with cefradine show two to four times more activity than cefradine alone against methicillin-sensitive Staphylococcus aureus(MSSA) and Klebsiella pneumoniae. The data suggest that the sulfenimine moiety may be beneficial to the activity and selectivity of inhibitors. |
| |
| Keywords: | β-Lactamase-inhibitor Sulfenimine Cephalosporins |
|
| 点击此处可从《高等学校化学研究》浏览原始摘要信息 |
|
点击此处可从《高等学校化学研究》下载全文 |
|
