1,3-Substituted β-Carboline Derivatives as Potent Chemotherapy for the Treatment of Cystic Echinococcosis
Echinococcosis is a global public health issue that generally occurs in areas with developed animal husbandry. In search of safe and effective therapeutic agents against echinococcosis, we designed and synthesized new 1,3-substituted β-carboline derivatives based on harmine. Among them, compounds 1a, 1c, and 1e displayed potent inhibitory activity against Echinococcus granulosus in vitro, significantly better than albendazole and harmine. The morphological detection revealed that 1a, 1c, and 1e significantly changed the ultrastructure of Echinococcus granulosus protoscolices (PSCs). Furthermore, pharmacokinetic studies suggested that 1a possessed a better metabolic property. Encouragingly, 1a exhibited a highest cyst inhibition rate as 76.8% in vivo and did not display neurotoxicity in mice. Further mechanistic research illustrated that 1a has the potential to induce autophagy in PSCs, which may be responsible for the therapeutic effect of the drugs. Together, 1a could be a promising therapeutic agent against echinococcosis, warranting further study.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:66 |
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| Enthalten in: |
Journal of medicinal chemistry - 66(2023), 24 vom: 28. Dez., Seite 16680-16693 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Bei [VerfasserIn] |
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| Links: |
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| Themen: |
4FHH5G48T7 |
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| Anmerkungen: |
Date Completed 29.12.2023 Date Revised 01.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jmedchem.3c01326 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM365606286 |
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| 520 | |a Echinococcosis is a global public health issue that generally occurs in areas with developed animal husbandry. In search of safe and effective therapeutic agents against echinococcosis, we designed and synthesized new 1,3-substituted β-carboline derivatives based on harmine. Among them, compounds 1a, 1c, and 1e displayed potent inhibitory activity against Echinococcus granulosus in vitro, significantly better than albendazole and harmine. The morphological detection revealed that 1a, 1c, and 1e significantly changed the ultrastructure of Echinococcus granulosus protoscolices (PSCs). Furthermore, pharmacokinetic studies suggested that 1a possessed a better metabolic property. Encouragingly, 1a exhibited a highest cyst inhibition rate as 76.8% in vivo and did not display neurotoxicity in mice. Further mechanistic research illustrated that 1a has the potential to induce autophagy in PSCs, which may be responsible for the therapeutic effect of the drugs. Together, 1a could be a promising therapeutic agent against echinococcosis, warranting further study | ||
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| 700 | 1 | |a Wu, Jianbing |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Zhengsheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Hongmei |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Huijing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yihua |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Jingxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Zhangjian |e verfasserin |4 aut | |
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