Filaricidal Activity of Substituted Phenyl Arsenoxides

Abstract

The filaricidal activity of the substituted phenyl arsenoxides was studied. The group of drugs had an in vitro activity against the microfilaria of Dirofilaria immitis 10-300 times that of the most active of the antimony compds. tested. Within the group there was a 30-fold difference between the least active and the most active, whereas there was scarcely more than a 3-fold difference in the acute toxicities for mice. The amide substituted compds., such as those with the p-CONR2 or p-SONR2 substitution, killed the microfilariae at the highest dilutions. Among 6 phenyl arsenoxides given intraperit. to cotton rats in doses of 0.9 mg. As/kg, b.i.d. for 25 and 45 days, all showed some activity; 4 amide substituted compds. used reduced the microfilaria blood levels 70-90% during treatment, and three of them killed 90-100% of the adult worms. Only p-arsenosobenzamide among these compds. killed all the adult worms in half the above daily dose for the same length of time and reduced the microfilaria blood level 50-80%. Since the compd. is very insoluble, work with it was discontinued. Compds. were studied in which organic radicals were substituted for O2 in the p-arsenosobenzamide. The dithioglycollate substituted compd. offered promise of both solubility and a favorable therapeutic index. It killed all adult worms in cotton rats receiving 0.9 mg. As/kg. b.i.d. intraperit. for 6 wks. but failed to reduce the microfilaria level. Intraven. injn. into dogs infected with D. immitis also failed to reduce the microfilaria level. The drug was effective against the adult worms in daily doses of 0.23 mg. As/kg. for at least 2 wks. In man, the same doses appear to be feasible.