EFFECTS ON PROTOZOA 739 



Relation of Arsenical Structure to Activity 



As we have observed with regard to toxicity, very few siibstituent groups 

 increase the parasiticidal activity of phenylarsenoxide and no marked in- 

 creases occur at all; on the other hand, the activity is often greatly de- 

 creased. A summary of the results of Eagle and his collaborators is given in 

 Table 6-12. Eagle and Doak (1951) divided the substituent groups into four 

 general classes and the relative activities and parasiticidal/toxic ratios 

 are averaged in the accompanying tabulation, with full realization that 

 there is much variation within the groups. The inert groups include 



NO.3, CH3, CI, NH2, OH, and F; the slightly active include KNHg, ROH, 

 NHCOCH3, RNHCOCH3, and OCOCH3; the acidic groups include COOH, 

 SO3H, and RCOOH; and the amides include CONH2, RCONH2, and 

 SO2NH2. The inert groups may slightly reduce the activity and toxicity 

 but do not significantly alter the ratio, while the slightly active groups exert 

 a moderate effect on both. The acidic groups quite markedly reduce all 

 types of activity, but the parasiticidal more than the toxic, and hence the 

 ratio falls, whereas the amides are relatively less toxic as shown by the de- 

 finitely high ratios. Therapeutically one would, of course, desire a high 

 ratio. As usual, there are exceptional cases; thus the 3-NH2-4-OH-9^-AsO, 

 or oxophenarsine, although containing two inert groups, not only exhibits 

 a high ratio but is also clinically useful. 



Derivatives with acidic groups form an interesting class, not only be- 

 cause of their marked reduction in activity, but also because of the surpris- 

 ing effects which are dependent on chain length. That activity is reduced 

 is not surprising, since one might expect negatively charged molecules to 

 penetrate less readily; this effect is more pronounced for the protozoa. 

 Esterification of these acidic groups restores the activity toward normal 

 as expected; however, the formation of an amide group has the odd effect 

 of further reducing the toxicity while increasing the parasiticidal activity 

 compared to the free acidic compounds. Differences in the permeability 

 properties of host and parasite cells are evident here. The differences between 

 the compounds with COOH groups on different positions of the ring can 



