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
A series of sulfenimine cephalosporin sulfoxide derivatives (Ta-v) were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested c...A series of sulfenimine cephalosporin sulfoxide derivatives (Ta-v) were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C β-lactamase cephalospor- inase compared with the tazobactam. The most promising compounds 7c and 7n (IC50 ~ 7.6 and 8.6 μmol/L, respectively) were further investigated in combination with cefradine against a variety of clinical isolated fi-lactamase-producing bacterial strains.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.
文摘A series of sulfenimine cephalosporin sulfoxide derivatives (Ta-v) were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C β-lactamase cephalospor- inase compared with the tazobactam. The most promising compounds 7c and 7n (IC50 ~ 7.6 and 8.6 μmol/L, respectively) were further investigated in combination with cefradine against a variety of clinical isolated fi-lactamase-producing bacterial strains.