Inhibitory effect of isoquinoline alkaloids on movement of second-stage larvae of Toxocara canis

To find new anthelmintics against parasites living in host tissues, we used an in vitro assay to screen isoquinoline alkaloids for nematocidal activity on the larva of dog roundworm, Toxocara canis. To evaluate the efficacy of anthelmintics in vitro, Tsuda et al. previously introduced the concept of Relative Mobility (RM) of Toxocara larvae. After improvement of the assay system using image data processing, we generated a new index, RM50, the concentration at which RM=50%. However, except for pyrantel, the RM, of most existing anthelmintics could not be calculated because of low activity. Of the isoquinoline alkaloids tested, emetine, sanguinarine, 6-methoxydihydrosanguinarine (6-MS), chelerythrine and berberine showed strong nematocidal activities. However, these compounds were highly cytotoxic; thus, the prospect of their direct application is low. We then tested the cytotoxicity (IC50) of other isoquinoline alkaloids in HL60 tissue-culture cells. We continued our search for new anthelmintics by examining in detail the relationship between RM50 and IC50. We determined that an ideal target compound would exhibit a low RM50/IC50 ratio. Allocryptopine, dehydrocorydaline and papaverine were identified as potentially effective anthelmintics.