Ferrocenyl-cephalosporin

Fig. 3 Organometallic complexes of known organic antiproliferation agents designed to overcome drug resistance a ferrocenyl-penicillin derivatives b ferrocenyl-cephalosporin derivatives c rhodium chloroquine complex d ferrocenjd-chloroquine derivative e iri-dium-COD-pentamidine complex...

One of the first appHcations of this approach was an attempt to resolve, at least temporarily, the problem of the acquired resistance to antibiotics of certain bacteria. These bacteria produce p-lactamase which degrades antibiotics of the peniciUin or cephalosporin type. Edwards et al. [38—41] developed a series of ferrocenyl-peniciUins 5 and ferrocenyl-cephalosporins 6 as p-lactamase inhibitors, in which the initial aromatic group was replaced by a ferrocene entity. Some representative examples are shown below (Scheme 3.2). 

Edwards El, Epton R, Marr G (1976) 1, l -Ferrocenyldiacetic acid anhydride and its use in the preparation of heteroannularly substituted ferrocenyl-penicillins and -cephalosporins. J Organomet Chem 122 C49-C53... 

When the ferrocenyl group is situated too dose sterically to the p-lactam nudeus, where R = FcC(O)-, no antibiotic activity is observed for the modified penicillins and cephalosporins. However, the addition of a methylene spacer to distance the ferrocenyl moiety from the p-lactam nudeus restores the antibiotic activity to the same high levd as that of the controls (Penicillin G and methidUin). Replacement of the methylene by CMe2 increases p-lactamase inhibition and decreases the antibiotic activity. For a recent and exhaustive review of metallic antibiotics in general, see Ming [10]. 

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