Importance of functional groups in determining drug actions and toxicity

10 Importance of functional groups in determining drug actions and toxicity 

To date, over 10 000 structural analogues of sulphanilamide, the parent of all sulpha drugs, have been synthesized and used in the SAR studies. However, only about 40 of them have ever been used as prescribed drugs. Sulpha drugs are bactereostatic, i.e. they inhibit bacterial growth but do not actively kill bacteria. These drugs act on the biosynthetic pathway of tetrahydrofolic acid, inhibit dihydropteroate synthetase and mimic the shape of PABA (para-aminobenzoic acid). 

From numerous studies, it has now been established that the amino functional groups (—NH2) is essential for the activity. In addition, the following structural features have to be present in sulpha drugs for the optimum antibacterial activity. 

The structure of Prontosil, an azo dye, is quite similar to the structure of sulphanilamide with the modification that the — NH2 is substituted. As result, it does not have any in vitro antibacterial activity, but in vivo Prontosil is converted via reduction of the —N=N— linkage to its active metabolite sulphanilamide. 

A-heterocyclic derivatives of sulphanilamide, e.g. sulphadiazine, sul-phathiazole and sulphoxazole, have broad-spectrum antimicrobial activity. They are generally more water soluble, and thus better absorbed and retained better, i.e. excreted slowly. 

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