THE TOXICITY AND TREPONEMICIDAL ACTIVITY OF AMIDESUBSTITUTED PHENYL ARSENOXIDES AND THEIR DERIVATIVES

¹ From the Venereal Disease Research and Postgraduate Training Center of the U. S. Public Health Service, Johns Hopkins Hospital, Baltimore—5, Maryland

Thirteen amide-substituted phenyl arsenoxides (-RCONH₂, -RSO₂NH₂) were, per unit arsenic, only 4.5 to 13.5 per cent as toxic as the parent phenyl arsenoxide. Since the treponemicidal activity in vitro was not reduced to the same degree, the ratio of treponemicidal activity: toxicity was 1.9 to 6.1 times more favorable than that of phenyl arsenoxide. The favorable effect of amide groups was confirmed for ten of these compounds by assays of toxicity and therapeutic activity in syphilitic rabbits.

When one or both of the amide hydrogens were substituted (e.g., -SO₂N(CH₃), -CONH-pyridine), the effect of the entire group shifted toward that of the terminal substituent. In most cases, substitution in the amide therefore caused an increased toxicity, and impaired the favorable effect of the amide group as such. Only in the case of the compounds with terminal hydroxyl acetamido or nitrile groups was the favorable effect of the amide altogether preserved, perhaps because these groups in themselves depress the toxicity of phenyl arsenoxide.

The regularity with which substituents containing terminal amide groups decreased the toxicity and increased the chemotherapeutic index of phenyl arsenoxide suggests that some members of this series may be of clinical utility.