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Tytuł:
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Evaluation of ursolic acid derivatives with potential anti-Toxoplasma gondii activity.
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Autorzy:
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Zhang LH; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133002, China.
Jin LL; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133002, China.
Liu F; Department of Pharmacy, Yanbian University Hospital, Yanji, 133002, China.
Jin C; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133002, China.
Jin CM; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133002, China. Electronic address: .
Wei ZY; Medical College of Dalian University, Dalian, 116622, China. Electronic address: .
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Źródło:
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Experimental parasitology [Exp Parasitol] 2020 Sep; Vol. 216, pp. 107935. Date of Electronic Publication: 2020 Jun 20.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Orlando, FL : Academic Press
Original Publication: New York.
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MeSH Terms:
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Anti-Infective Agents/*pharmacology
Toxoplasma/*drug effects
Toxoplasmosis/*drug therapy
Toxoplasmosis, Animal/*drug therapy
Triterpenes/*pharmacology
Alanine Transaminase/blood ; Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/therapeutic use ; Aspartate Aminotransferases/blood ; Coccidiostats/chemistry ; Coccidiostats/pharmacology ; Disease Models, Animal ; Female ; Glutathione/metabolism ; Liver/drug effects ; Liver/enzymology ; Liver/pathology ; Malondialdehyde/metabolism ; Mice ; Molecular Docking Simulation ; Organ Size/drug effects ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases ; Random Allocation ; Spiramycin/pharmacology ; Spleen/drug effects ; Spleen/pathology ; Triterpenes/chemistry ; Triterpenes/therapeutic use ; Ursolic Acid
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Contributed Indexing:
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Keywords: Anti-T. gondii; Docking; TgCDPK1 inhibitors; Ursolic acid; in vitro; in vivo
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Substance Nomenclature:
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0 (Anti-Infective Agents)
0 (Coccidiostats)
0 (Protein Kinase Inhibitors)
0 (Triterpenes)
4Y8F71G49Q (Malondialdehyde)
8025-81-8 (Spiramycin)
EC 2.6.1.1 (Aspartate Aminotransferases)
EC 2.6.1.2 (Alanine Transaminase)
EC 2.7.- (Protein Kinases)
GAN16C9B8O (Glutathione)
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Entry Date(s):
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Date Created: 20200623 Date Completed: 20200902 Latest Revision: 20231213
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Update Code:
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20240105
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DOI:
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10.1016/j.exppara.2020.107935
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PMID:
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32569599
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Toxoplasma gondii is an important pathogen that causes serious public health problems. Currently, therapeutic drugs for toxoplasmosis cause serious side effects, and more effective and novel substances with relatively low toxicity are urgently needed. Ursolic acid (UA) has many properties that can be beneficial to healthcare. In this study, we synthesized eight series of UA derivatives bearing a tetrazole moiety and evaluated their anti-T. gondii activity in vitro using spiramycin as a positive control. Most of the synthesized derivatives exhibited better anti-T. gondii activity in vitro than UA, among which compound 12a exhibited the most potent anti-T. gondii activity. Furthermore, the results of biochemical parameter determination indicated that 12a effectively restored the normal body weight of mice infected with T. gondii, reduced hepatotoxicity, and exerted significant anti-oxidative effects compared with the findings for spiramycin. Additionally, our molecular docking study indicated that the synthesized compounds could act as potential inhibitors of T. gondii calcium-dependent protein kinase 1 (TgCDPK1), with 12a possessing strong affinity for TgCDPK1 via binding to the key amino acids GLU129 and TYR131.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
