Solutions For An Introduction to Medicinal Chemistry Chapter 19 Problem 7Q

Cephalosporins and penicillin both belong to the same group of antibiotics termed as β-lactam antibiotics. The characteristic feature of such antibiotics is the presence of a β-lactam ring in their structure.

They are a broad class of antibiotics, which act by inhibiting the bacterial cell wall synthesis, specifically the synthesis of the peptidoglycan layer of the cell wall. They act as analogues of D-alanyl-D-alanine, a part of the precursor peptide units of this layer.

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The major difference between the structures of the cephalosporin compounds and the penicillin compounds lies in the nature of the ring structures attached to their β-lactam subunits.

On the one hand, cephalosporins contain dihydrothiazine, an unsaturated six-membered ring, attached to their β-lactam unit. While on the other hand, penicillin molecules are characterized by thiazolidine, a five-membered saturated ring, fused to their β-lactam unit.

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In both the cephalosporins and the penicillin molecules, the bicyclic ring system offers a great strain to the β-lactam ring, which is considered to be important for the activity of the molecule. Although due to the dihydrothiazine ring, this strain is much less in cephalosporins as compared to the penicillin molecules.

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This kind of structure offers various advantages to cephalosporins over penicillin, in that they are more stable in acidic conditions and in the presence of β-lactamase enzyme. Also, cephalosporins have an affinity for a broader range of bacterial species as compared to the penicillin, although the activity of the former may be lower than the latter.