Role of the NH 2,OH and As = As Groups in Parasitotoxic Action of Arsphenamine Derivatives

Abstract

Some of the derivatives of arsphenamine differ from one another considerably in their in vitro toxicity towards trypanosomes but are more alike in their chemotherapeutic activity. The reasons for this are probably manifold. The chemotherapeutically active compounds may be of the RAsO type (Ehrlich, 1 Voegtlin and Smith 2 ) and the rates of formation of the substituted arsenious oxides from the RAs = AsR forms may differ, Mayer 3 and Maschmann 4 have suggested that the in vitro toxicity is due mainly to the other groups substituted on the benzol ring.

In order to draw conclusions as to the role of single groups in the toxicity, we have compared the toxic action of neoarsphenamine on Trypanosoma equiperdum, and also the color reaction of the drug with osmic acid, with the same properties of compounds of the RAsO type, lacking one or both of the substituted groups, OH and NH₂ possessed by the arsenious oxide corresponding to arsphenamine.

The reaction of neoarsphenamine with osmic acid (Hiramatsu 5 ). To attempt to determine the amount of unchanged neoarsphenamine in a solution of the same exposed to the air, we used Hiramatsu's osmic acid colorimetric method, claimed by the author to determine quantitatively small amounts of neoarsphenamine even in the presence of protein. That a purple color is given by unoxidized solutions of neoarsphenamine or of 3-amino-4-hydroxyphenylarsenious oxide (“Arsenoxide”) was confirmed. It was further observed that the reaction can be prevented by the addition of sufficient sodium thioglycollate (a few drops of M/20 NaOOCCH₂SH in about 2 cc. of M/2000 neoarsphenamine or “Arsenoxide”). Although the color is probably due to the formation of colloidal osmium after reduction of osmic acid by the arsenical, the inhibition of reaction by thioglycollate was first interpreted as an action on the —As = As— or the —AsO groups (formation of thioarsenites, Cohen, King and Strange ways 6 ).