Beta-lactam antibiotics

Dinuclear Cobalt(II) Complexes as Metallo‐β‐lactamase Mimics

“…[2] Whereas the most widely used therapeutic agents against bacterial infections are β-lactams, [2,3] metallo-β-lactamases (MβL) have emerged as a major contributor to antibiotic resistance in rapidly {k 1 = [(2.5 ϫ 10 3 ) Ϯ (1.9 ϫ 10 1 )] M -1 min -1 } than its subsequent hydrolysis {k 2 = [(1.6 ϫ 10 -1 ) Ϯ (8.1 ϫ 10 -4 )] min -1 }. [2,3,5] Furthermore, whereas for the metal-independent serine-β-lactamases clinically useful inhibitors are available, the same is not true for MβLs. For [Co 2 (CO 2 EtL2)-(CH 3 COO) 2 ] + , only one relevant pK a1 (8.47 Ϯ 0.14) is evident, assigned to a terminal water molecule.…”

Metallo‐β‐lactamases and Their Biomimetic Complexes

“…terial infections, [2,3] the increased use of antibiotics means that bacteria are constantly evolving their ability to inactivate these antibiotic drugs. [3] The mode of action of βlactam antibiotics comprises diffusion through the outer membrane of the bacterial cells and inhibition of transpeptidases, which are essential for cell wall biosynthesis.…”

“…[14][15][16] The subclass B1 MβLs are dimetallic enzymes with one zinc(II) ion in a tetrahedral arrangement with three histidine ligands and a water/hydroxo ligand bridging to the second zinc(II) ion (this site is termed the histidine site). [2,3,5,31] Cephalothin and nitrocefin belong to the class of cephalosporin lactams, the former being the first cephalosporin antibiotic to be commercially used. Mononuclear forms of B1 enzymes (i.e.…”

“…This second metal ion has a trigonal pyramidal arrangement in the so-called cysteine site composed of an aspartate, a cysteine, a histidine, and two water/hydroxo molecules, one of which bridges to the metal in the histidine site. [2,32] While not used therapeutically, nitrocefin has been extensively em-ployed in MβL assays as it undergoes a distinctive color change upon hydrolysis which can be monitored spectrophotometrically. BcII from Bacillus subtilis) are known, and in these the metal ion is located in the histidine site.…”

“…BcII from Bacillus subtilis) are known, and in these the metal ion is located in the histidine site. [2] While classes A, C, and D can be inhibited in their action, there is to date no clinical useful inhibitor for MβLs. In this subclass the catalytic metal ion is in the cysteine site.…”