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KMID : 0351619760170010046
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Kyungpook Medical Journal
1976 Volume.17 No. 1 p.46 ~ p.55
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Therapeutic Effects of Niclofolan Derivatives on Experimental Clonorchiasis Rabbits and its Toxicity
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Koh Kyung-Hwan
Kim Jong-Suk
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Abstract
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Niclofolan(5, 5´-Dichloro-2, 2´-Dihydroxy-3, 3´-Dinitro Biphenyl) has been used in the treatmen of fascioliasis in animals and it was proved to be effective for paragonimiasis and clonorchiasi3 in man, However, because of it´s side effect and toxicity it lias remained in clinical trial stage. In this study, as one of the efforts to find out a less toxiy drug from the niclofolan analogous it was. attempted to know the structure activity relationship, especially, the role of the nitro grou in the structure of niclofolan for the therapeutic effect and toxicity. For this purpose, three compounds. niclofolan, aniclofolan and amiclofolan, were compared fo therapeutic effect and toxicity. In the rabbits artificially infected with Clonorchis sinensis thereapeutic effects were observed wi niclofolan(Smg/kg/day for 3 days) highly effective, aniclofolan (SOmg/kg/day) less effective, whip Amiclofolan ineffective, orally. In vitro test, one hundred percent of vermicidal effect; was observed with niclofolan in cony centration of 10-Sg/ml within 12 hrs and with aniclofolan 10´"´g/ml within 36 hrs. Whereas, fift percent cf vermicidal effect was observed with amiclofolan iii the concentration of 10-4g/ml within 48hrs. Infu.ion of mclofolan(0.63mg/kg/min) and a iclofol (3.15mg/kg/min)intothe vein of rabbit it caused gradual stimulation of respiration follo~ved by depresion and a suden death after 15 and 4d minutes cf infusion respectively. In the group infused with amiclofolan (3.15mg/kg/min), it also caused gradual elevation of blood pressure, but the rabbits remain alive even after 80 minuts oi´ infusion, and also respiration was stimulated slightly. On the isolated rabbit intestine, niclofolan analogous caused gradual decrease in tonus and amplitude of movement and then finally complete ceastion of motility. The concentration pf these drugs; in which caused cessation of motility within a few minutes were 5 X 10-´g/ml of niclofclofolan, LO-g/ml of aniclofolan and 5X10-5g/ml of amiclofolan. In the five rabbits given niclolofolan in a dose of 20mg/kg/~iay for 3 days, the rabbits becam excited at an early stage and was depressed later and one of the five animals was expired. Ele ation of GOT in two rabbits and GPT in one rabbit were noted, but there was no significan histological change in the kidney and the liver in any of the rabbits. In those groups received niclofolan (lOmg/kg/day),, or aniclofolan (50mg/kg/day) for 6 days re:spectiveIy, no behavioral changes were noted during t:he treatment. Even after treatment, no aIternation were noted in the serum total protein, alkaline phosphatase, GOT, GPT and histological finding in the liver and the kidney. With the above result, it can be summerized that niclofolan which has two nitro group in the structure, has the most potency in the respect to therapeutic effect of clonorchiasis and toxicity. A:miclofolan which has tow amino group, has the least Effect and toxicity Aniclofolan which has or.~e nitro and one amino group be placed between them.
Fram these results, it suggest that the presence of nitro group in the structure of niclofolan is indispensable for the therapeautic effect of cIonorchiasis and toxicity.
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KEYWORD
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