816 



SCIENCE 



[N. S. Vol. XXXII. No. 832 



NH ■ CH.CO 



I 



I /ONa 

 As=0 

 \0H 



Atosyl contains a diazotizable NHj group 

 and only one Na. It is possible to prepare 

 azodyestnffs from atoxyl by diazotizing 

 and combining it with the usual amines 

 and acids, and to introduce acyl radicles 

 into the amido group. 



To Wendelstaedt belongs the credit of 

 having shown that an entirely different 

 class of colors is capable, even in exceed- 

 ingly small doses, of causing a temporary 

 disappearance of the trypanosomes, al- 

 though possessing no definite curative ac- 

 tion. 



The chief objections to the use of these 

 colors of the malachite- and brilliant-green 

 group are, however, their rather injurious 

 and irritating properties. Various at- 

 tempts were made to diminish these by ex- 

 perimenting with derivatives of these 

 colors. 



Wendelstaedt found, as Ehrlich had pre- 

 viously demonstrated with various groups 

 of chemicals — phenols, alkaloids and dye- 

 stuffs — that although sulfo derivatives were 

 devoid of toxicity, they unfortunately 

 lacked any destructive action upon the 

 parasite. When Ehrlich took up experi- 

 ments with the malachite-green colors he 

 remembered from his previous experience 

 with fuchsin colors, that by alkylation the 

 irritating effect was materially enhanced. 

 He therefore attributed the toxicity of 

 malachite- and brilliant-green to the pres- 

 ence of the four methyl groups in the first 

 and the four ethyl groups in the latter 

 substance. Having previously also demon- 

 strated that the carboxyl groups, like the 

 sulfo groups, deprived these substances of 

 their parasitieidal power, he concluded 



that by acid groups the malachite- and 

 brilliant-green colors were, in fact, modi- 

 fied in the desired manner, but that the car- 

 boxyl- and sulfo-groups were too radical in 

 their action, and that perhaps by the in- 

 troduction of a faintly acid group the tox- 

 icity would be lessened without oblitera- 

 tion of the parasitieidal effect. As such a 

 faintly acid group the hydroxyl group sug- 

 gested itself to him, and he prepared ortho-, 

 meta- and para-oxy-malachite-green, the 

 di- and tri-oxy-malachite-green, and found, 

 indeed, that they were less toxic than 

 malachite-green, retaining, however, strong 

 parasitieidal action. By combining some 

 of the hydroxyl derivatives of malachite 

 green with the trypanred treatment he 

 succeeded in curing nagana infection when 

 trypanred alone only prolonged life. 



Ehrlich tried all kinds of rosanilin de- 

 rivatives from the most complicated form 

 of ortho-tri-oxy-hexa-methylpararosanilin 

 down to the simplest pararosanilin (para- 

 fuchsin), and found that the latter best 

 served his purpose. He therefore made all 

 future experiments with this substance. 

 In reviewing his tests he came to the con- 

 elusion that the best results were obtained 

 when he fed mice for two days with cake 

 containing parafuchsin, and then inocu- 

 lated them with trypanosoma. This treat- 

 ment caused the disappearance of the para- 

 sites of nagana, dourine and caderas for 

 seven to twelve days, and proved superior 

 to injections, which caused considerable 

 irritation of the skin. As the mice, how- 

 ever, refused to eat cake impregnated with 

 parafuchsin, it was found necessary to con- 

 vert it into a difficultly soluble salt, such as 

 the oleate with an excess of oleic acid. 

 Some mice could be fed in this way for 

 months without any impairment of health. 

 If the infection was intense the feeding 

 was preceded by an injection of fuchsin or 

 atoxyl. 



