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Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential

Ischemic stroke is a common neurological disease that can lead to mortality and disability. The current curative effect remains unsatisfactory because drug accumulation in the diseased areas is insufficient as a result of the unique blood–brain barrier. Therefore, much attention has been paid to dev...

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Autores principales: Zhang, Jing, Jiang, Miaomiao, Zhao, Hui, Han, Lan, Jin, Yu, Chen, Weidong, Wang, Jianqing, Zhang, Ziyu, Peng, Can
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883289/
https://www.ncbi.nlm.nih.gov/pubmed/33597878
http://dx.doi.org/10.3389/fphar.2020.608221
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author Zhang, Jing
Jiang, Miaomiao
Zhao, Hui
Han, Lan
Jin, Yu
Chen, Weidong
Wang, Jianqing
Zhang, Ziyu
Peng, Can
author_facet Zhang, Jing
Jiang, Miaomiao
Zhao, Hui
Han, Lan
Jin, Yu
Chen, Weidong
Wang, Jianqing
Zhang, Ziyu
Peng, Can
author_sort Zhang, Jing
collection PubMed
description Ischemic stroke is a common neurological disease that can lead to mortality and disability. The current curative effect remains unsatisfactory because drug accumulation in the diseased areas is insufficient as a result of the unique blood–brain barrier. Therefore, much attention has been paid to develop a novel therapeutic compound, paeonol-ozagrel conjugate (POC), for ischemic stroke. Then, POC was successfully synthesized by conjugating of paeonol and ozagrel as mutual prodrug. A series of in vitro characterizations and evaluations, including high - resolution mass spectroscopy, nuclear magnetic resonance spectroscopy, partition coefficient, and assessment of cytotoxicity against PC12 cells, were performed. Pharmacokinetic study demonstrated POC is eliminated quickly (t(1/2) = 53.46 ± 19.64 min), which supported a short dosing interval. The neurological score, infarct volume, histopathological changes, oxidative stress, inflammatory cytokines levels, and TXA(2) levels also were evaluated in vivo in middle cerebral artery occlusion (MCAO) rats. All results showed that POC had a significant curative and therapeutic effect on ischemic stroke, as evaluated by the middle cerebral artery occlusion. Overall, POC can be expected to become a new drug candidate for the treatment of ischemic stroke.
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spelling pubmed-78832892021-02-16 Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential Zhang, Jing Jiang, Miaomiao Zhao, Hui Han, Lan Jin, Yu Chen, Weidong Wang, Jianqing Zhang, Ziyu Peng, Can Front Pharmacol Pharmacology Ischemic stroke is a common neurological disease that can lead to mortality and disability. The current curative effect remains unsatisfactory because drug accumulation in the diseased areas is insufficient as a result of the unique blood–brain barrier. Therefore, much attention has been paid to develop a novel therapeutic compound, paeonol-ozagrel conjugate (POC), for ischemic stroke. Then, POC was successfully synthesized by conjugating of paeonol and ozagrel as mutual prodrug. A series of in vitro characterizations and evaluations, including high - resolution mass spectroscopy, nuclear magnetic resonance spectroscopy, partition coefficient, and assessment of cytotoxicity against PC12 cells, were performed. Pharmacokinetic study demonstrated POC is eliminated quickly (t(1/2) = 53.46 ± 19.64 min), which supported a short dosing interval. The neurological score, infarct volume, histopathological changes, oxidative stress, inflammatory cytokines levels, and TXA(2) levels also were evaluated in vivo in middle cerebral artery occlusion (MCAO) rats. All results showed that POC had a significant curative and therapeutic effect on ischemic stroke, as evaluated by the middle cerebral artery occlusion. Overall, POC can be expected to become a new drug candidate for the treatment of ischemic stroke. Frontiers Media S.A. 2021-02-01 /pmc/articles/PMC7883289/ /pubmed/33597878 http://dx.doi.org/10.3389/fphar.2020.608221 Text en Copyright © 2021 Zhang, Jiang, Zhao, Han, Jin, Chen, Wang, Zhang and Peng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Jing
Jiang, Miaomiao
Zhao, Hui
Han, Lan
Jin, Yu
Chen, Weidong
Wang, Jianqing
Zhang, Ziyu
Peng, Can
Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential
title Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential
title_full Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential
title_fullStr Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential
title_full_unstemmed Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential
title_short Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential
title_sort synthesis of paeonol-ozagrel conjugate: structure characterization and in vivo anti-ischemic stroke potential
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883289/
https://www.ncbi.nlm.nih.gov/pubmed/33597878
http://dx.doi.org/10.3389/fphar.2020.608221
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