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, RM(50), the concentration at which RM=50%. However, except for pyrantel, the RM(50) 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 (IC(50)) of other isoquinoline alkaloids in HL60 tissue-culture cells. We continued our search for new anthelmintics by examining in detail the relationship between RM(50) and IC(50). We determined that an ideal target compound would exhibit a low RM(50)/IC(50) ratio. Allocryptopine, dehydrocorydaline and papaverine were identified as potentially effective anthelmintics.
Satou
Tadaaki
T
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Kobe, Japan.
Akao
Nobuaki
N
Matsuhashi
Rinako
R
Koike
Kazuo
K
Fujita
Koichiro
K
Nikaido
Tamotsu
T
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D018922:HL-60 Cells; D006801:Humans; D007546:Isoquinolines / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D007814:Larva / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D018514:Plant Structures; D017166:Toxocara canis / Q000187:drug effects* / Q000254:growth & development
D000470:Alkaloids; D007546:Isoquinolines; D010936:Plant Extracts; C039109:isoquinoline