Trypanocidal action and toxicity to enzymes

Abstract

Trypan-blue, trypan-red, and Bayer 205 are toxic to fumarase. The toxicity of 6 naphthylaminedisulfonic acids and their s-carbamide derivatives on fumarase were investigated. The free acids and their first s-carbamide derivatives were inert. Toxicity began to be apparent with the 2nd carbamide derivatives (s-carbamide of m-aminobenzoyl-naphthylaminedisulfonic acid) and was very marked with the 3rd carbamide derivatives (s-carbamide of m-aminobenzoyl-m-aminobenzoyl-naphthyl-aminedisulfonic acid). Attention is drawn to the parallelism which exists between this effect and trypanocidal action which begins only at the second s-carbamide stage of combination and is most marked at the third s-carbamide stage. The parallelism with the substantive properties of these derivatives to cotton is also discussed, and it is shown that there must be some structure in common between the fumarase enzyme, cotton fibre and the trypanosome which makes for specific combination or adsorption with the 2nd and 3rd s-carbamide derivatives of the naphthylaminedisulfonic acids. These derivatives are not toxic to urease. Derivatives of the 2-naph-thylaminedisulfonic acids are much more toxic to fumarase than those of the 1-naphthylaminedisulfonic acids. Fumarate "protected" the enzyme, fumarase, from the toxic action of these derivatives.