title: Assay of nematocidal activity of isoquinoline alkaloids using third-stage larvae of Strongyloides ratti and S. venezuelensis.
abstract: 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 (PC(50)). 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 (IC(50)) 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 PC(50)/IC(50) 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 PC(50)/IC(50) 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.
authors.affiliation: Department of Pharmacognosy, School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Satou
authors.forename: Masataka
authors.initials: M
authors.lastname: Koga
authors.forename: Rinako
authors.initials: R
authors.lastname: Matsuhashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
authors.forename: Isao
authors.initials: I
authors.lastname: Tada
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Nikaido
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007814:Larva; D007928:Lethal Dose 50; D021261:Parasitic Sensitivity Tests / Q000662:veterinary; D013321:Strongyloides / Q000187:drug effects* / Q000254:growth & development; D017171:Strongyloides stercoralis / Q000187:drug effects; D013322:Strongyloidiasis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000470:Alkaloids; D000969:Antinematodal Agents; D007546:Isoquinolines