D F Avgustinovich1,2, M A Tsyganov3,4, M Y Pakharukova3, E N Chulakov5, A V Dushkin6,7, V P Krasnov5, V A Mordvinov8. 1. Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russian Federation. avgust@bionet.nsc.ru. 2. Institute of Solid State Chemistry and Mechanochemistry, SB RAS, Kutateladze Str. 18, Novosibirsk, 630128, Russian Federation. avgust@bionet.nsc.ru. 3. Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russian Federation. 4. Novosibirsk State University, Pirogova Str. 10, Novosibirsk, 630090, Russian Federation. 5. Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences (UB RAS), S. Kovalevskoy Str. 22/Academic Str. 20, Ekaterinburg, 620990, Russian Federation. 6. Institute of Solid State Chemistry and Mechanochemistry, SB RAS, Kutateladze Str. 18, Novosibirsk, 630128, Russian Federation. 7. National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China. 8. Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russian Federation. mordvin@bionet.nsc.ru.
Abstract
BACKGROUND: 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:Na2GA, 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. METHODS: 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. RESULTS: The O. felineus maritae that received PZQ:Na2GA (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. CONCLUSION: 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.
BACKGROUND: 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:Na2GA, 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. METHODS: 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. RESULTS: The O. felineus maritae that received PZQ:Na2GA (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. CONCLUSION: 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.
Entities:
Keywords:
(R)-PZQ and (S)-PZQ; Disodium glycyrrhizinate; Opisthorchis felineus; Praziquantel
Authors: Vinícius Barros Ribeiro da Silva; Bruna Rafaella Koresch Leiva Campos; Jamerson Ferreira de Oliveira; Jean-Luc Decout; Maria do Carmo Alves de Lima Journal: Bioorg Med Chem Date: 2017-04-27 Impact factor: 3.641
Authors: Ruiping Kong; Xingyi Zhu; Elizaveta S Meteleva; Yulia S Chistyachenko; Lyubov P Suntsova; Nikolay E Polyakov; Mikhail V Khvostov; Dmitry S Baev; Tatjana G Tolstikova; Jianming Yu; Alexander V Dushkin; Weike Su Journal: Int J Pharm Date: 2017-10-06 Impact factor: 5.875
Authors: Alexandra Probst; Daniela Hofmann; Olga S Fedorova; Sofia V Mazeina; Tatiana S Sokolova; Ekaterina Golovach; Jennifer Keiser Journal: Antimicrob Agents Chemother Date: 2022-09-12 Impact factor: 5.938