Journal of Antimicrobial Chemotherapy (1999) 44, 729-734
© 1999 The British Society for Antimicrobial Chemotherapy
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ß-Lactams: variations on a chemical theme, with some surprising biological results
Department of Medical Microbiology, Royal Free and University College Medical School, London, UK
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Introduction |
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Until the middle of the 1970s virtually all the significant developments in ß-lactam antibiotics had been achieved by adding different side chains to the classical penam and cephem nuclei.1
Notwithstanding the fact that, in earlier decades, manipulation of the penicillin nucleus had
failed to
produce any novel drugs of interest,2 the second half of the
1970s saw huge progress in useful alterations to the basic penam and cephem ring structures.
Penems (Ia) were synthesized,3 naturally occurring
carbapenems
(Ib, e.g. olivanic acids), oxapenams and monocyclic ß-lactams (nocardicins and
monobactams) were discovered,4 ,5 ,6 ,7 and
penam sulphones (II) were found to be inhibitors of some ß-lactamases.8 The cephalosporin nucleus was modified to produce microbiologically
active oxacephems9 (IIIa) and carbacephems (IIIb).10 Not all changes were advantageous: for
example,
oxocephems (IV),11 cephams (V)12 and cephems with the double bond in the 2,3
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Modifications |
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Antifungal activity
Compounds with a modified ß-lactam ring
Compounds with extra rings
Interactions with g-aminobutyric acid (GABA)
Inhibition of human and viral serine proteases
Inhibition of human cytosolic phospholipase A2
Inhibition of HIV protease
Delivery of anticancer drugs
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Conclusions |
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Notes |
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References |
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