Avgustinovich D F, Tsyganov M A, Pakharukova M Y, Chulakov E N, Dushkin A V, Krasnov V P, Mordvinov V A
Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russian Federation.
Institute of Solid State Chemistry and Mechanochemistry, SB RAS, Kutateladze Str. 18, Novosibirsk, 630128, Russian Federation.
Acta Parasitol. 2020 Mar;65(1):156-164. doi: 10.2478/s11686-019-00149-2. Epub 2019 Dec 3.
Nowadays, it is still important to develop effective anti-opisthorchiasis agents. In this work, we tested a complex of praziquantel (PZQ) with a plant origin compound-disodium glycyrrhizinate-in the ratio 1:10 PZQ:NaGA, containing 11-fold less of the active ingredient. Our aim was to study various ways to treat trematode Opisthorchis felineus with this complex in vitro. Additionally, an in vitro comparison of the anthelmintic action was made among racemic-PZQ, (R)-PZQ, and (S)-PZQ on juvenile and adult maritae of O. felineus.
Worms extracted from the hamsters were subjected to various regimens of administration of the complex: once a day for 3 days or three times within 1 day. Moreover, mature maritae and juvenile worms of O. felineus were subjected to the comparison the anthelmintic effectiveness of racemic-PZQ, (R)-PZQ, and (S)-PZQ.
The O. felineus maritae that received PZQ:NaGA (1:10) thrice within 1 day were most strongly affected by the drug. Their motility substantially decreased already on the second day after the last dose, and the percentage of live worms by the end of the experimental period was the lowest. These results indicate a cumulative anthelmintic effect of this substance under the regimen "three times within 1 day." For the first time, we report that among the three substances (racemic-PZQ and two enantiomers), (R)-PZQ has the highest anthelmintic activity, toward both juvenile and sexually mature maritae of O. felineus.
These findings suggest that the development of a supramolecular complex of (R)-PZQ with disodium glycyrrhizinate and administration of this complex three times within 1 day are promising approaches.
如今,开发有效的抗华支睾吸虫病药物仍然很重要。在这项研究中,我们测试了吡喹酮(PZQ)与一种植物源化合物——甘草酸二钠——以PZQ:NaGA为1:10比例组成的复合物,其活性成分含量减少了11倍。我们的目的是研究用这种复合物在体外治疗猫后睾吸虫的各种方法。此外,还对消旋PZQ、(R)-PZQ和(S)-PZQ对猫后睾吸虫幼虫和成虫的驱虫作用进行了体外比较。
从仓鼠体内提取的虫体接受该复合物的不同给药方案:每天一次,共3天,或在1天内给药3次。此外,对猫后睾吸虫的成熟成虫和幼虫进行了消旋PZQ、(R)-PZQ和(S)-PZQ驱虫效果的比较。
在1天内接受3次PZQ:NaGA(1:10)的猫后睾吸虫成虫受药物影响最强烈。在最后一剂后的第二天,它们的活力就大幅下降,到实验期结束时活虫的百分比最低。这些结果表明该物质在“1天内给药3次”方案下具有累积驱虫效果。我们首次报告,在这三种物质(消旋PZQ和两种对映体)中,(R)-PZQ对猫后睾吸虫的幼虫和性成熟成虫具有最高的驱虫活性。
这些发现表明,开发(R)-PZQ与甘草酸二钠的超分子复合物并在1天内给药3次是有前景的方法。