Assay of nematocidal activity of isoquinoline alkaloids using third-stage larvae of Strongyloides ratti and S-venezuelensis

We examined the effects of isoquinoline alkaloids in vitro in an effort to identify a treatment for Strongyloides stercoralis larva migrans in humans. Infective third-stage larvae of S. ratti and S. venezuelensis were used as model nematodes for S. stercoralis. Nematocidal activity was evaluated by the 50% paralysis concentration (PC50). Most of the tested isoquinoline alkaloids had activity for S. ratti and S. venezuelensis. We then evaluated in vitro cytotoxicity, which was the 50% inhibition concentration (IC50) of the compounds using HL60 tissue-culture cells. Three of the compounds (protopine, D-corydaline, and L-stylopine) which exhibited strong nematocidal activity, showed little cytotoxicity. In addition, we examined the relationship between nematocidal activity and cytotoxicity using the PC50/IC50 ratio. A ratio equivalent to or lower than that calculated for the currently prescribed strongyloidosis treatments, ivermectin, albendazole and thiabendazole, was observed for allocryptopine, protopine, dehydrocorydaline, D-corydaline, L-Stylopine, and papaverine. In contrast, the PC50/IC50 ratios for protopine, D-corydaline, and L-stylopine were substantially more favorable. Therefore, protopine, D-corydaline, and L-stylopine were identified as potential effective treatments for strongyloidosis. (C) 2002 Elsevier Science B.V All rights reserved.