Synthesis, Molecular Docking, c-Met Inhibitions of 2,2,2-Trichloroethylidene- cyclohexane-1, 3-dione Derivatives Together with their Application as Target SARS-CoV-2 main Protease (Mpro) and as Potential anti-COVID-19
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro).
OBJECTIVE: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti- COVID-19 treatment, this study lays the groundwork for further experimental research to investigate these compounds' efficacy and potential medical uses to treat COVID-19.
METHODS: New heterocyclic compounds were synthesized through the first reaction of cyclohexane- 1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to produce biologically active compounds.
RESULTS: Novel compounds, including fused thiophene, pyrimidine and pyran derivatives, were synthesized and tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti-COVID-19 target molecules.
CONCLUSION: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty-two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h showed that all compounds exhibited higher inhibitions than the reference Foretinib.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Combinatorial chemistry & high throughput screening - 26(2023), 7 vom: 29., Seite 1437-1449 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Almutairi, Fahad M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.04.2023 Date Revised 25.04.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1386207325666220829111236 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM345611357 |
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| 100 | 1 | |a Almutairi, Fahad M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Synthesis, Molecular Docking, c-Met Inhibitions of 2,2,2-Trichloroethylidene- cyclohexane-1, 3-dione Derivatives Together with their Application as Target SARS-CoV-2 main Protease (Mpro) and as Potential anti-COVID-19 |
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| 500 | |a Date Completed 12.04.2023 | ||
| 500 | |a Date Revised 25.04.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro) | ||
| 520 | |a OBJECTIVE: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti- COVID-19 treatment, this study lays the groundwork for further experimental research to investigate these compounds' efficacy and potential medical uses to treat COVID-19 | ||
| 520 | |a METHODS: New heterocyclic compounds were synthesized through the first reaction of cyclohexane- 1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to produce biologically active compounds | ||
| 520 | |a RESULTS: Novel compounds, including fused thiophene, pyrimidine and pyran derivatives, were synthesized and tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti-COVID-19 target molecules | ||
| 520 | |a CONCLUSION: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty-two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h showed that all compounds exhibited higher inhibitions than the reference Foretinib | ||
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| 650 | 4 | |a M | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Trichloroethylidene | |
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| 650 | 4 | |a molecular docking | |
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| 650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
| 650 | 7 | |a Cyclohexanes |2 NLM | |
| 650 | 7 | |a Protease Inhibitors |2 NLM | |
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| 700 | 1 | |a Wardakhan, Wagnat W |e verfasserin |4 aut | |
| 700 | 1 | |a Mohamed, Mervat S |e verfasserin |4 aut | |
| 700 | 1 | |a Abdelhameed, Ali S |e verfasserin |4 aut | |
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