ARSENICALS 



139' 



brain are inhibited. Simple monothiols combine with aromatic arsene oxides and 

 might be expected to protect enzyme sulphydryl groups but the combination is 

 readily dissociated (Cohen, King and Strangeways, 1931). 



Further advances have followed as the result of war-time researches. (Peters 

 and Wakelin, 1946 ; Stocken and Thompson, 1946 ; Barron, Miller and Bartlett, 

 1947 ; Danielli et al., 1947.) Arsenic compounds are not only chemotherapeutic 

 ao'ents but are also potential war gases and vesicants. It has been found that the 

 toxic effect of arsenic can be neutralised by dithiols such as 2 : 3-dimercaptopro- 

 panol (BAL or British Anti-Lewisite) or it? glucoside which form much more stable 

 cyclic compounds than the monothiols with arsenic. The dithiols can compete 

 successfully with protein SH Compounds for the arsenic and hence can protect 

 them or even regenerate SH groups which have combined with arsenic. Enzyme- 

 systems can thus escape inhibition in the presence of arsenical compounds. 



A result of these observations is that the possibility arises of reducing the toxicity 

 to patients of therapeutic arsenicals (e.g., mapharside) without impairing the 

 therapeutic efficency since the arsenic compound may be dissociated locally to 

 produce its chemotherapeutic effect. (Peters and Stocken, 1947.) On the other- 

 hand it has been shown (Webb and van Heyningen, 1947 ; Barron, Miller and Meyer, 

 1947) that dithiol compounds themselves inhibit some enzyme systems by combining 

 with heavy metals forming the prosthetic group, by reducing the rate of oxidation 

 of cytochrome-C. and by inhibiting certain SH enzymes. Thus the dithiol com- 

 pounds might not only reduce the toxicity of the therapeutic arsenicals to the host 

 but might themselves have a chemotherapeutic effect by inhibiting enzyme systems 

 of the infecting organisms. On the other hand the disadvantages of administering 

 dithiols at the same time as arsenical chemotherapeutic agents would be that they 

 might both reduce the inhibiting effect on the infecting parasites and yet damage-- 

 the host by interfering with tissue enzyme systems. 



TABLE 25 

 Half Wave Potentials of Phenylarsonic Acids 

 (volts vs. saturated calomel electrode) 



Breyer (1939) measured the half-wave potentials of a series of phenyl arsonic- 

 acids polarographically, and found that the introduction of substitutents increased 

 the ease of reduction, but was unable to find a correlation between the oxidation- 

 reduction potential and toxicity. 



