Conformations cephalosporin

Studies on the mode of action of the penicillins in inhibiting bacterial cell-wall biosynthesis suggest that the members of this class of antibiotics (including the closely related cephalosporins) are conformationally restricted substrate analogs... 

Some cephalosporins can be both substrates and inhibitors of /3-lactamases. The acyl-enzyme intermediate can undergo either rapid deacylation (Fig. 5.4, Pathway a) or elimination of the leaving group at the 3 -position to yield a second acyl-enzyme derivative (Fig. 5.4, Pathway b), which hydrolyzes very slowly [35][53], Thus, cephalosporins inactivate /3-lactamases by a mechanism similar to that described above for class-II inhibitors. It has been hypothesized that differences in the rate of deacylation of the acyl-enzyme intermediates derive from their different abilities to form H-bonds. A H-bond to NH in Fig. 5.4, Pathway a, may be necessary to assure a catalytically essential conformation of the enzyme, whereas the presence of a H-bond acceptor in Fig. 5.4, Pathway b, may drive the enzyme to an unproductive conformation. The ratio between hydrolysis and elimination, and, consequently, the relative importance of substrate and inhibitor behaviors of cephalosporins, is determined by the nature of the leaving group at C(3 ). An appropriate substitution at C(3 ) of cephalosporins may, therefore, increase the /3-lactamase inhibitory properties and yield potentially better antibiotics [53]. 

Emulsion liquid membrane extraction of cephalosporins conform to the type II facilitated transport. Here the solute transport is either associated with a cotransport or counter-transport of an anionic species depending on whether ion-pair or ion-exchange extraction is exploited in the ELM system. 

Peritonitis due to ruptured viscus Conforms, fragilis Metronidazole + cephalosporin (third-generation), piperacillin/tazobactam Carbapenem, tigecycline... 

Copper(II) binds some 10-fold more strongly to cephalosporins than to penicillins.411,414 Molecular models indicate that one of the conformations of cephalosporins would be very suitable for binding via the carboxylate group and the /8-lactam carbonyl oxygen (124) giving rise to a seven-membered chelate ring. Variations in the /3-lactam carbonyl stretching frequency on com-plexation provide some support for structure (124). 

There have been a number of hypotheses regarding the mode of action of /8-lactam antibiotics [237,238]. That most widely used at present is the structural analogue hypothesis [183,215], based on the structural similarity between penicillins and a possible conformation of the acyl-D-alanyl-D-alanine end of the N-acetylmuramyl-pentapeptide strand of the bacterial cell wall. A number of experimental data support this hypothesis (for recent reviews see [237] and [238]) and the model attractively explains the mechanism of action of /3-lactam antibiotics, especially penicillins. Nevertheless, certain more recent data contradict the structural analogue model [239-241] and a conformational response model has been set up [242,243]. It must be emphasized, however, that the contradictions are sometimes only apparent, and a one-sided interpretation of the structure-activity data may lead to false conclusions, e.g. the problem of the 6(7)a-substitution in penicillins and cephalosporins. 

The differences in conformation of penicillin, A - and ALcephems and cephams have already been studied by different methods [39,267-270]. The steric position of the 3-carboxy group in penicillins is closer to that in A -cephems than to that in A -cephems. On the other hand, the bridgehead nitrogen atom of penicillins and A -cephalosporins is definitely pyramidal, in contrast to its planar structure in A -cephems and cephams Table 8.29) [269]. /3-lactams fused with 7 or 8 membered rings (compounds... 

Cation radicals in mass spectrometry, 526 Cellobiose, 991-992 Cellulose, 994 Cembrene, 1027 Center of symmetry, 264—265 in meso-2,3-butanediol, 280 Cephalexin, 803 Cephalosporins, 803 Cerebrosides, 1047 Chair conformation... 

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