Antibacterial Agents 5. Antimetabolites and Synthetic Drugs

  • David Edwards


Antimetabolite chemotherapy came of age when Woods in 1940 demonstrated that the sulphonamide sulphanilamide competed with PABA for the enzyme responsible for folate synthesis in bacteria. This was a key discovery because it opened the way to chemotherapy based on the synthesis of molecules which were structural and functional analogues of key metabolites of the cell. Generally, chemotherapy based on antimetabolites has not been the success it was initially envisaged, since antimetabolites, which proved good inhibitors of bacterial growth in vitro, failed to perform as expected in vivo. The reasons for this are many and include the fact that since most of them are competitive inhibitors of a cell reaction the inhibition causes the substrate of the inhibited enzyme to build up until concentrations are reached which overcome the block. A second, equally important, feature of antimetabolites is that for the most part they are small highly soluble molecules which are eliminated from the blood very rapidly, making it difficult to achieve prolonged and adequate blood levels necessary for the therapeutic effect.


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10.10 References and Further Reading

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© David Edwards 1980

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  • David Edwards

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