Satou Tadaaki, Koga Masataka, Matsuhashi Rinako, Koike Kazuo, Tada Isao, Nikaido Tamotsu
Department of Pharmacognosy, School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Vet Parasitol. 2002 Mar 1;104(2):131-8. doi: 10.1016/s0304-4017(01)00619-7.
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.
我们在体外研究了异喹啉生物碱的作用，以期找到一种治疗人体粪类圆线虫幼虫移行症的方法。用鼠类圆线虫和委内瑞拉类圆线虫的感染性三期幼虫作为粪类圆线虫的模型线虫。通过50%麻痹浓度（PC(50)）评估杀线虫活性。大多数受试异喹啉生物碱对鼠类圆线虫和委内瑞拉类圆线虫有活性。然后我们评估了体外细胞毒性，即使用HL60组织培养细胞测定化合物的50%抑制浓度（IC(50)）。三种表现出强杀线虫活性的化合物（原阿片碱、D-紫堇碱和L-刺罂粟碱）显示出很小的细胞毒性。此外，我们使用PC(50)/IC(50)比值研究了杀线虫活性与细胞毒性之间的关系。对于别隐品碱、原阿片碱、脱氢紫堇碱、D-紫堇碱、L-刺罂粟碱和罂粟碱，观察到该比值等于或低于目前规定的类圆线虫病治疗药物伊维菌素、阿苯达唑和噻苯达唑所计算出的比值。相比之下，原阿片碱、D-紫堇碱和L-刺罂粟碱的PC(50)/IC(50)比值则更为有利。因此，原阿片碱、D-紫堇碱和L-刺罂粟碱被确定为类圆线虫病的潜在有效治疗药物。
