Anthelmintic Natural Products against Clonorchis sinensis and the Analogues

간디스토마에 작용하는 천연물 및 그 유사체

Among 230 species of herbal drugs screened, thirty one show the anthelmintic activities in vitro against Clonorchis sinensis, the chinese liver fluke. The active substances have been isolated and their structures identified. Some of the active substances and their derivatives have been synthesized, followed by anthelmintic activity tests. The extracts from the active drugs cause damages in organs of the adult worm in the hepatic duct of rabbit. Some fresh water fish, which function as bad hosts for the fluke, excrete defense substances against the cercaria of the fluke. The defense substances have been isolated from Cyprinus carpio and Cyprinus carpio nudus, followed by structural identification. The results are summarized as follows: l) The bark of Machilus thunbergii as well as the seed of Schizandra chinensis contain meso-dihydro-guaiaretic acid as the anthelmintic component. Among derivatives synthesized, 4-phenyl-1-((3, 4-dihydroxyphenyl)-, 4-phenyl-1-(3-hydroxy-4-methoxy phenyl)-and 4-phenyl-1-(4-hydroxy-3-methoxy phenyl)-2, 3-dimethyl butanes show considerable activities. Administration of the bark extract mainly damages the bladder of the adult worm. 2) The active substance from the roasted fruit of Prunus mume is 2-hydroxymethylfurfural. This substance is produced during the roasting process. Administration of the fruitextract causes a damage of the bladder of the adult worm. 3) The active substance from the root of Scutellaria baicalensis is 5.2'-dihydroxy-6, 7, 8, 6'-tetramethoxyflavone. 4) Beside alantolactone, a very strong anthelmintic component is contained in the root of Inula helenium. Administration of the root extract causes irreversible damage on the worm, affecting mainly the reproductive organs. 5) The cercaricidal substances from the epidermis of C. carpio and C. carpio nudus are ethyl linoleate and linoleic acid, respertively. 6) The cercaricidal substances from various kinds of fresh water fish have different $R_f$ values, implying that the defense substances are species-specific. Unexpectedly, the fish with good host function, for example Pseudorasbora parva, excrete the defense substances, too. The defense substances are possibly organ-specific in individual species; the organs essenstial for the existence of the species excrete the defense substances, allowing other parts to be invaded by the cercaria. 7) The cercaricidal fraction of Carassius carassius is detected only in the fish which have been collected during the summer time from May to September, Its secretion is not dependent on water temperature. Thus, it seems to be possible that the secretion of the defense substance would be stimulated through a contact between the fish and cercaria.