One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach
Although antimicrobial resistance before the Covid-19 pandemic is a top priority for global public health, research is already ongoing on novel organic compounds with antimicrobial and antiviral properties in changing medical environments in connection with Covid 19. Thanks to the Biginelli reaction...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222005469 |
| _version_ | 1811337355377770496 |
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| author | Youness El Bakri Malahat Musrat Kurbanova Sabir Ali Siddique Sajjad Ahmad Souraya Goumri-Said |
| author_facet | Youness El Bakri Malahat Musrat Kurbanova Sabir Ali Siddique Sajjad Ahmad Souraya Goumri-Said |
| author_sort | Youness El Bakri |
| collection | DOAJ |
| description | Although antimicrobial resistance before the Covid-19 pandemic is a top priority for global public health, research is already ongoing on novel organic compounds with antimicrobial and antiviral properties in changing medical environments in connection with Covid 19. Thanks to the Biginelli reaction, which allows the synthesis of pyrimidine compounds, blockers of calcium channels, antibodies, antiviral, antimicrobial, anti-inflammatory, or antioxidant therapeutic compounds were investigated. In this paper, we aim to present Biginelli's synthesis, its therapeutic properties, and the structural–functional relationship in the test compounds that allows the synthesis of antimicrobial compounds. Both the DFT and TD-DFT computations of spectral data, molecular orbitals (HOMO, LUMO) analysis, and electrostatic potential (MEP) surfaces are carried out as an add-on to synthetic research. Hirshfeld surface analysis was also used to segregate the different intermolecular hydrogen bonds involved in the molecular packing strength. Natural Bond Orbital (NBO) investigation endorses the existence of intermolecular interactions mediated by lone pair, bonding, and anti-bonding orbitals. The dipole moment, linear polarizability, and first hyperpolarizabilities have been explored as molecular parameters. All findings based on DFT exhibit the best consistency with experimental findings, implying that synthesized molecules are highly stable. To better understand the binding mechanism of the SARS-CoV-2 Mpro, we performed molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations. |
| first_indexed | 2024-04-13T17:53:41Z |
| format | Article |
| id | doaj.art-ced16d90be394353a51ea16691fffe07 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-13T17:53:41Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-ced16d90be394353a51ea16691fffe072022-12-22T02:36:36ZengElsevierArabian Journal of Chemistry1878-53522022-11-011511104230One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approachYouness El Bakri0Malahat Musrat Kurbanova1Sabir Ali Siddique2Sajjad Ahmad3Souraya Goumri-Said4Department of Theoretical and Applied Chemistry, South Ural State University, Lenin prospect 76, Chelyabinsk 454080, Russian Federation; Corresponding authors.Baku State University, Organic Chemistry Department, Z. Khalilov 23, Baku, AZ 1148, AzerbaijanCenter for Organic Chemistry, School of Chemistry, University of the Punjab, Lahore 54590, PakistanDepartment of Health and Biological Sciences, Abasyn University, Peshawar 25000, PakistanCollege of Science, Physics department, Alfaisal University, Riyadh 11533, Saudi Arabia; Corresponding authors.Although antimicrobial resistance before the Covid-19 pandemic is a top priority for global public health, research is already ongoing on novel organic compounds with antimicrobial and antiviral properties in changing medical environments in connection with Covid 19. Thanks to the Biginelli reaction, which allows the synthesis of pyrimidine compounds, blockers of calcium channels, antibodies, antiviral, antimicrobial, anti-inflammatory, or antioxidant therapeutic compounds were investigated. In this paper, we aim to present Biginelli's synthesis, its therapeutic properties, and the structural–functional relationship in the test compounds that allows the synthesis of antimicrobial compounds. Both the DFT and TD-DFT computations of spectral data, molecular orbitals (HOMO, LUMO) analysis, and electrostatic potential (MEP) surfaces are carried out as an add-on to synthetic research. Hirshfeld surface analysis was also used to segregate the different intermolecular hydrogen bonds involved in the molecular packing strength. Natural Bond Orbital (NBO) investigation endorses the existence of intermolecular interactions mediated by lone pair, bonding, and anti-bonding orbitals. The dipole moment, linear polarizability, and first hyperpolarizabilities have been explored as molecular parameters. All findings based on DFT exhibit the best consistency with experimental findings, implying that synthesized molecules are highly stable. To better understand the binding mechanism of the SARS-CoV-2 Mpro, we performed molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations.http://www.sciencedirect.com/science/article/pii/S1878535222005469DihydropyrimidinonesSARS-CoV-2 MproHirshfeld surface analysisNBO analysisMolecular docking |
| spellingShingle | Youness El Bakri Malahat Musrat Kurbanova Sabir Ali Siddique Sajjad Ahmad Souraya Goumri-Said One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach Arabian Journal of Chemistry Dihydropyrimidinones SARS-CoV-2 Mpro Hirshfeld surface analysis NBO analysis Molecular docking |
| title | One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach |
| title_full | One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach |
| title_fullStr | One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach |
| title_full_unstemmed | One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach |
| title_short | One-pot synthesis, X-ray crystal structure, and identification of potential molecules against COVID-19 main protease through structure-guided modeling and simulation approach |
| title_sort | one pot synthesis x ray crystal structure and identification of potential molecules against covid 19 main protease through structure guided modeling and simulation approach |
| topic | Dihydropyrimidinones SARS-CoV-2 Mpro Hirshfeld surface analysis NBO analysis Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222005469 |
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