Efficient synthesis of novel colchicine-magnolol hybrids and evaluation of their inhibitory activity on key proteases of 2019-nCoV replication and acute lung injury
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV), is a life-threatening infectious condition. Acute lung injury is a common complication in patients with COVID-19. 3-chymotrypsin-like protease (3CLpro) of 2019-nCoV and neutrophil elastase are critical targets of COVID-19 and acute lung injury, respectively. Colchicine and magnolol are reported to exert inhibitory effects on inflammatory response, the severe comorbidity in both COVID-19 and acute lung injury. We thus designed and synthesized a series of novel colchicine-magnolol hybrids based on a two-step synthetic sequence. It was found that these novel hybrids provided unexpected inhibition on 3CLpro and neutrophil elastase, a bioactivity that colchicine and magnolol did not possess. These findings not only provide perquisites for further in vitro and in vivo investigation to confirm the therapeutic potentiality of novel colchicine-magnolol hybrids, but also suggest that the concurrent inhibition of 3CLpro and neutrophil elastase may enable novel colchicine-magnolol hybrids as effective multi-target drug compounds.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Natural product research - 38(2024), 7 vom: 27. März, Seite 1238-1247 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pu, Liu-Yang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.03.2024 Date Revised 14.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/14786419.2022.2138870 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV), is a life-threatening infectious condition. Acute lung injury is a common complication in patients with COVID-19. 3-chymotrypsin-like protease (3CLpro) of 2019-nCoV and neutrophil elastase are critical targets of COVID-19 and acute lung injury, respectively. Colchicine and magnolol are reported to exert inhibitory effects on inflammatory response, the severe comorbidity in both COVID-19 and acute lung injury. We thus designed and synthesized a series of novel colchicine-magnolol hybrids based on a two-step synthetic sequence. It was found that these novel hybrids provided unexpected inhibition on 3CLpro and neutrophil elastase, a bioactivity that colchicine and magnolol did not possess. These findings not only provide perquisites for further in vitro and in vivo investigation to confirm the therapeutic potentiality of novel colchicine-magnolol hybrids, but also suggest that the concurrent inhibition of 3CLpro and neutrophil elastase may enable novel colchicine-magnolol hybrids as effective multi-target drug compounds | ||
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| 700 | 1 | |a Ma, Yucui |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Shengquan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Zhengzhi |e verfasserin |4 aut | |
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