144 



OXIDATION-REDUCTION POTENTIALS 



Prontosil 



N=N-/ \s 



O2NH2 



NH2/ \ 



SO2NH2 



Sulphonilamide 



In 1938, Whitby showed that sulphapyridine prepared by May and Baker was 

 effective against pneumococcal infections and numerous other sulpha-drugs have 

 been prepared since. Not only have many lives been saved by these drugs but an 

 active stimulus was jDrovided for chemotherapeutic research generally and probably 

 assisted in the rapid development of antibiotics. The successful use of sulphonamide 

 encouraged workers to investigate its mode of action and here again the stimulus has 

 been effective outside the realm of the sulpha-drugs and practical therapeutics 

 stretching into fundamental fields. 



It was soon found that the presence of peptones and various cell extracts antag- 

 onised and inhibited the bactericidal effect of sulphonamide in vitro (Stamp, Green), 

 and this effect was traced to the presence of p-aminobenzoic acid (Woods). It will be 

 recalled that p-aminobenzoic acid is a constitutent of folic acid (pteroyl-glutamic 

 acid) the growth factor for Lactobacillus casei which stimulates blood regeneration in 

 certain types of anaemia. 



STRUCTURAL ANALOGUE INHIBITION 



It is established that at least part of the bactericidal effect of sulphonamide is 

 to interfere in some way with the need of certain bacteria for p-aminobenzoic acid. 

 The structural relation of sulphonamide (ii) with p-aminobenzoic acid (i) and foHc acid 

 (iii) is indicated below : — 



NH, 



0) 



(H) 



lutamatc 



