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 （...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 gmol/L, respectively） were fur- ther investigated against a series of clinical isolated β-lactamase-producing bacterial strains. The results reveal that compounds 6c and 60 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.展开更多
文摘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 gmol/L, respectively） were fur- ther investigated against a series of clinical isolated β-lactamase-producing bacterial strains. The results reveal that compounds 6c and 60 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.
