Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>)
A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide <b>2</b> with various carbonyl compounds. Also, dehydrative-cyclocondensation of <b>2</b> with active methylene compounds or anhydrides gave the respe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/19/4565 |
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| author | Sraa Abu-Melha Mastoura M. Edrees Sayed M. Riyadh Mohamad R. Abdelaziz Abdo A. Elfiky Sobhi M. Gomha |
| author_facet | Sraa Abu-Melha Mastoura M. Edrees Sayed M. Riyadh Mohamad R. Abdelaziz Abdo A. Elfiky Sobhi M. Gomha |
| author_sort | Sraa Abu-Melha |
| collection | DOAJ |
| description | A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide <b>2</b> with various carbonyl compounds. Also, dehydrative-cyclocondensation of <b>2</b> with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (M<sup>pro</sup>) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds <b>3a</b>, <b>3b</b>, and <b>3c</b> (−8.1 ± 0.33 kcal/mol, −8.0 ± 0.35 kcal/mol, and −8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (−6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle. |
| first_indexed | 2024-03-10T15:49:04Z |
| format | Article |
| id | doaj.art-aabf11fcc3a9441eb0ad5471f0813f77 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:49:04Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-aabf11fcc3a9441eb0ad5471f0813f772023-11-20T16:14:18ZengMDPI AGMolecules1420-30492020-10-012519456510.3390/molecules25194565Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>)Sraa Abu-Melha0Mastoura M. Edrees1Sayed M. Riyadh2Mohamad R. Abdelaziz3Abdo A. Elfiky4Sobhi M. Gomha5Department of Chemistry, Faculty of Science, King Khalid University, Abha 61413, Saudi ArabiaDepartment of Chemistry, Faculty of Science, King Khalid University, Abha 61413, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, MIU University, Cairo 19648, EgyptBiophysics Department, Faculty of Science, Cairo University, Giza 12613, EgyptDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613, EgyptA novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide <b>2</b> with various carbonyl compounds. Also, dehydrative-cyclocondensation of <b>2</b> with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (M<sup>pro</sup>) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds <b>3a</b>, <b>3b</b>, and <b>3c</b> (−8.1 ± 0.33 kcal/mol, −8.0 ± 0.35 kcal/mol, and −8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (−6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.https://www.mdpi.com/1420-3049/25/19/4565hydrazidehydrazonecondensationcyclo-condensationdockingSARS-CoV-2 M<sup>pro</sup> |
| spellingShingle | Sraa Abu-Melha Mastoura M. Edrees Sayed M. Riyadh Mohamad R. Abdelaziz Abdo A. Elfiky Sobhi M. Gomha Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>) Molecules hydrazide hydrazone condensation cyclo-condensation docking SARS-CoV-2 M<sup>pro</sup> |
| title | Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>) |
| title_full | Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>) |
| title_fullStr | Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>) |
| title_full_unstemmed | Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>) |
| title_short | Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M<sup>pro</sup>) |
| title_sort | clean grinding technique a facile synthesis and in silico antiviral activity of hydrazones pyrazoles and pyrazines bearing thiazole moiety against sars cov 2 main protease m sup pro sup |
| topic | hydrazide hydrazone condensation cyclo-condensation docking SARS-CoV-2 M<sup>pro</sup> |
| url | https://www.mdpi.com/1420-3049/25/19/4565 |
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