Effect on Biological Activity of Substituting Sulphur for Oxygen in an Organic Arsenical Compound.

Abstract

Voegtlin and his associates 1 have called attention to the significance of sulphur metabolism in connection with arsenic toxicity. It seemed of interest to determine the effect on biological activity of substituting sulphur for oxygen in an organic arsenical compound where this substitution is possible. We approached this problem from our particular standpoint of the chemotherapy of amebiasis, determining toxicity on oral administration to cats and rabbits, and amebacidal activity in vitro on Entameba histolytica, employing technique described elsewhere, 2 except that we used a Musgrave-Clegg slant and Ringer's solution containing albumen and rice-starch with pH adjusted to lie between 7.4 and 7.6, in an effort to prevent absorption of the drug by the solid medium.

Through the courtesy of the Lilly Research Laboratories, we secured 4-carbaminophenyl-arsonic acid (H₂O₃As.C₆H₄.NHCONH₂) and 4-thiocarbamino-phenyl-arsonic acid (H₂O₃As.C₆H₄.NHCSNH₂), which differ from each other in that the latter contains sulphur instead of oxygen in the carbamide radicle. The actual arsenic content of the former agreed closely with theory, but there was only 18.7% arsenic in the thio compound instead of the theoretical 27.1%. It seems impossible to prepare this substance with an arsenic content much closer to the theoretical. The comparison of the two drugs was further complicated by the fact that the thio compound was much less soluble than the other even in alkaline solution.

We found, however, that thiocarbaminophenyl-arsonic acid is only about a fourth as toxic on oral administration to rabbits and cats as carbaminophenyl-arsonic acid, and that it is only about one-sixth as powerful an amebacidal agent in vitro. A summary of our data, with figures for sodium acetarsone as a standard for calculating therapeutic indices, is given in Table I.