Abstract

A nitrovinylfuran derivative, trans-5-amino-3-[2-(5-nitro-2-furyl)-vinyl]-1,2,4-oxadiazole (SQ 18,506), exerted high chemotherapeutic activity when administered p.o. to mice and hamsters infected with Schistosoma mansoni, resulting consistently in parasitologic cures. Antischistosomal effectiveness was increased when the particle size of the compound was reduced to 3 to 5 µ but further decrease in the particle size did not enhance efficacy. The latter was improved by coadministration with glycerol. Parasitologic cures were also observed after the i.m. injection of a single high dose of SQ 18,506. Although the desnitro analog was completely inactive, antischistosomal activity was maintained when one or two methyl groups or an acetyl group were attached to the amino group on the oxadiazole ring. Similarly, the desamino analog had high activity; however, its toxicity was much greater than that of SQ 18,506. The latter also had considerable activity against Schistosoma japonicum and its administration had a direct destructive effect on schistosome eggs deposited in the tissues of the host. Evidence was obtained that strains of schistosomes resistant to SQ 18,506 do not develop readily. There appeared to be a lack of host toxicity with curative antischistosomal doses of SQ 18,506. Administration of subcurative doses of either niridazole or of SQ 18,506 results in reduced glycogen phosphorylase phosphatase activity of the parasite. This effect was more selective in the case of the nitrovinylfuran, however, because, in contrast to niridazole, administration of this compound, even in doses exceeding curative levels, had no effect on the activity of phosphorylase phosphatase of the host muscle.