Cephalosporins chemical structures

The effectiveness of penicillin in the treatment of infections prompted research directed toward finding new antibiotics with a wider range of antibacterial activity. The cephalosporins are a valuable group of drugp that are effective in the treatment of almost all of the strains of bacteria affected by the penicillins, as well as some strains of bacteria that have become resistant to penicillin. The cephalosporins are structurally and chemically related to penicillin. 

The large number and diversity of available /3-lactams, mainly penicillins and cephalosporins, necessitate their classification. Penicillins can be classified primarily according to chemical structure. Table 5.2 shows that there is good correspondence between chemical structure and properties. The categorization of cephalosporins into chemically similar groups is not useful because their antimicrobial spectrum is not closely correlated with chemical structure, and classification into generations is based on their spectrum of microbial activity (Table 5.3). 

When grouped on the basis of similarities in their chemical structure, most antibiotics fall into the categories listed in Table 1.17. S-Lactams, which include penicillins and cephalosporins, exhibit a characteristic /i-lactam core ring structure (a four-atom cyclic amide) (Figure 1.14). They induce their bacteriocidal activity by inhibiting the synthesis of peptidoglycan, an essential component of the bacterial cell wall. 

Loracarbef Lorabid) is a synthetic p-lactam antibiotic of the carbacephem class. The chemical structure of loracarbef is similar to that of cefaclor. Selected pharmacokinetic information appears in Table 45.2. Lora-carbef s spectrum of antibacterial activity resembles those of the second-generation cephalosporins. Comparative clinical trials reveal similar outcomes in patients treated with cefaclor, cefprozil, and loracarbef. 

In reality, the situation is more subde because very often the synthesis of direct analogues is justified by a desire to improve the existing drug. Thus, for penicillins the chemical structure that surrounds the beta-lactam ring is still being modified. Current antibiotics that have been derived from this research (e.g., the cephalosporins) are more selective, more active on resistant strains, and can be administered by the oral route. They are as different from the parent molecule as a recent car compared to a 40-year-old model In other words, innovation can result from the sum of a great number of stepwise improvements, as well as from a major breakthrough. 

Because penicillins and cephalosporins have a common chemical structure, cross-allergies occur with these drugs. Thus before initiating therapy with a penicillin. 

The cephalosporins are contraindicated in patients with known allergies or intolerances to any of the cephalosporins. Because the penicillins and cephalosporins have a common chemical structure, cross-allergies occur with these drugs. Thus before initiating therapy with a cephalosporin, careful inquiry should be made concerning previous hypersensitivity reactions to the other drugs. Because a secondary vitamin K deficiency can develop with cephalosporin use, the cephalosporins are contraindicated in patients with hemophilia. Cefaclor is also contraindicated in any patient with previous drug-related joint and skin reactions. 

Another long-acting parenteral cephalosporin of note is SK F 80303 (12). The semisynthetic oxacephalosporins are new chemical structures synthe-... 

This group of compounds includes both the penicillins and the cephalosporins for which the general chemical structures are shown in Fig. 11.9.1. Variation of Rj, R2 and R3 has allowed a number of chnically useful semisynthetic compounds to be synthesised. Ri, R2... 

Disulfiram-like reactions can occur in those who take cefaman-dole, cefmenoxime, cefoperazone, cefotetan, latamoxef (moxa-lactam) and possibly cefonicid, and drink alcohoL This is not a general reaction of the cephalosporins, but is confined to those with particular chemical structures. 

The principal types of cephalosporins will now be described. Table 13.2 gives the chemical structures, and International Names (note that many names now beginning ceP were formerly ceph ). 

Nowadays, antibiotics are primarily classified according to the mechanism of their action, with similarity of chemical structure as a secondary factor. Penicillin and its derivatives inhibit the formation of bacterial cell walls (Fig. 3.38). Cephalosporins have the same active mechanism. Other compounds are taken up into bacterial DNA to form unstable molecules (quinolones, metronidazole) or inhibit peptide synthesis (tetracychnes, aminoglycosides, macrolides). Some antibiotics (e.g. glycopeptides) exert a complex effect. 

This chapter has been written in order to familiarize the reader with the chemical structures of current and rare occupational allergens. For each molecule, the chemical structure and the Chemical Abstract Service (CAS) registry number are mentioned. One or several important literature references have been listed. However, it was not possible to be exhaustive, and some allergens have been omitted, since they were either obsolete, extremely rarely implicated in occupational contact dermatitis or because case reports were too imprecise. For some practical and chemical reasons, acrylates, beta-blocking agents, cephalosporins, methacrylates, organophosphorous compounds, penicillin derivatives, and pyridine and its derivatives have been listed in separated sections. 

Antigenic Determinants of Cephalosporins In vitro Studies of Chemical Structure-IgE Molecular Recognition Relationships. Chem Res Toxicol 2011 24 706. Adapted with permission from 2011 American Chemical Society... 

Montanez Ml, Mayorga C, Torres Ml, et al. Synthetic approach to gain insight into antigenic determinants of cephalosporins in vitro studies of chemical structure-IgE molecular recognition relationships. Chem Res Toxicol. 2011 24 706-17. 

---