Antischistosomal activity of aminoalkanethiols, aminoalkanethiosulfuric acids and the corresponding disulfides.

This paper discusses the development of a series of sulfur-containing compounds that show an interesting in vivo activity against infection by Schistosoma mansoni. These substances include the aminoalkanethiols, aminoalkanethiosulfuric acids and aminoalkyl disulfides, among others. Although the aminoethanethiols and their disulfide derivatives have presented a relatively high toxicity for the host animal, the aminoalkanethiosulfuric acids have a low toxicity and a high specificity for the adult female S. mansoni worms. In vitro studies with schistosomula, lung-phase schistosomula and adult worms have demonstrated effects on the tegument and the metabolism on these different stages of S. mansoni worms. The encapsulation of these drugs in a nanoemulsion has resulted in an increase in the in vitro activity.

Post-hepatectomy regeneration of the murine liver I. Effect upon Schistosoma mansoni lesions, before and after chemotherapy.

Hepatic histopathological changes due to Schistosoma mansoni infection in the mouse presented considerable improvement following partial hepatectomy, both during early (acute) and late (chronic) infections, and especially when surgery was preceded by curative chemotherapy. A 60% hepatectomy removed a great deal of a diseased liver that was replaced by a normal-looking tissue in which schistosomal lesions appeared fewer and scattered. After chemotherapy, residual fibrosis left either from cured acute and chronic schistosomal lesions, almost completely disappeared when the regenerated liver was examined a month afterwards. These marked changes, brought about by hepatectomy in experimental hepatic schistosomiasis, illustrate the fact that post-hepatectomy regeneration tends to restore the normal structure of the liver, even in a diseased organ.

A study of the activity of 2-(alkylamino)-1-phenyl-1-ethanethiosulfuric acids against infection by Schistosoma mansoni in a murine model.

The schistosomicidal activities of seven 2-(alkylamino)-1-phenyl-1-ethanethiosulfuric acids (1a-g) (R=propyl, isopropyl, butyl, isobutyl, t-butyl, sec-butyl, cyclohexyl, respectively) were determined in female Swiss mice infected with Schistosoma mansoni. The compounds were administered in a single oral dose of 800 mg/kg to groups of 15 mice infected with 50 cercariae each. All the compounds were found to be active, a high animal mortality being observed with 1e. These compounds have a high specificity against female worms (64-100% reduction vs. 33-61% reduction in male worms). The test was repeated, a 400-mg/kg sub-dose of 1f also being tested, and similar results were observed. A 94% reduction in the number of female worms was observed when compound 1c was administered in a single 800-mg/kg dose to animals infected with 80 cercariae. Finally, the test was repeated with single 800 mg/kg oral doses of compounds 1e (highly purified) and 1f and a 400-mg/kg sub-dose of 1c. The toxicity of 1e was confirmed, while the animals that received 1c and 1f presented reductions in the worm loads corresponding to 45.9% (male worms) and 84.8% (female worms) for 1c and 50.4% (male worms) and 94.2% (female worms) for 1f.