Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation
4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4H-chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidat...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024052526 |
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| author | Fathy M. Abdelrazek Magdi E.A. Zaki Sami A. Al-Hussain Basant Farag Ali M. Hebishy Mohamed S. Abdelfattah Safaa M. Hassan Ahmed F. El-Farargy Lyuba Iovkova David Mross Sobhi M. Gomha |
| author_facet | Fathy M. Abdelrazek Magdi E.A. Zaki Sami A. Al-Hussain Basant Farag Ali M. Hebishy Mohamed S. Abdelfattah Safaa M. Hassan Ahmed F. El-Farargy Lyuba Iovkova David Mross Sobhi M. Gomha |
| author_sort | Fathy M. Abdelrazek |
| collection | DOAJ |
| description | 4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4H-chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidated by analytical, spectral as well as X-ray crystallographic data. Heterocyclic compounds find widespread application in pharmaceutical and agrochemical products. Docking analyses were performed on the synthesized compounds to assess their binding modes with various amino acids of the target protein tubulin (PDB Code - 1SA0). The results indicated promising binding scores for compounds 4a and 4b, suggesting a strong affinity for the tubulin binding site. Finally, ADMET for the synthesized compounds 4a, 4b, 5, 8a and 8b were carried out. The drug likeness and pharmacokinetic properties of the prepared compounds were also evaluated. Notably, all of the novel compounds adhered to Lipinski's rule (Ro5) without any violations. |
| first_indexed | 2024-04-24T11:56:26Z |
| format | Article |
| id | doaj.art-58795c44d28d4dd399a6cf8e74977e8e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T11:56:26Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-58795c44d28d4dd399a6cf8e74977e8e2024-04-09T04:13:24ZengElsevierHeliyon2405-84402024-04-01107e29221Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidationFathy M. Abdelrazek0Magdi E.A. Zaki1Sami A. Al-Hussain2Basant Farag3Ali M. Hebishy4Mohamed S. Abdelfattah5Safaa M. Hassan6Ahmed F. El-Farargy7Lyuba Iovkova8David Mross9Sobhi M. Gomha10Chemistry Department, Faculty of Science, Cairo University, Giza, 12613, EgyptDepartment of Chemistry, Faculty of Science, Imam Mohammed Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Imam Mohammed Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, EgyptChemistry Department, Faculty of Science, Helwan University, Helwan, 11795, Cairo, EgyptChemistry Department, Faculty of Science, Helwan University, Helwan, 11795, Cairo, EgyptChemistry Department, Faculty of Science, Cairo University, Giza, 12613, Egypt; Chemistry Department, Faculty of Science, Helwan University, Helwan, 11795, Cairo, EgyptDepartment of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt; Fakultät für Chemie und Chemische Biologie, TU Dortmund, Dortmund, 44227, GermanyFakultät für Chemie und Chemische Biologie, TU Dortmund, Dortmund, 44227, GermanyFakultät für Chemie und Chemische Biologie, TU Dortmund, Dortmund, 44227, GermanyDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, Saudi Arabia; Corresponding author.4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4H-chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidated by analytical, spectral as well as X-ray crystallographic data. Heterocyclic compounds find widespread application in pharmaceutical and agrochemical products. Docking analyses were performed on the synthesized compounds to assess their binding modes with various amino acids of the target protein tubulin (PDB Code - 1SA0). The results indicated promising binding scores for compounds 4a and 4b, suggesting a strong affinity for the tubulin binding site. Finally, ADMET for the synthesized compounds 4a, 4b, 5, 8a and 8b were carried out. The drug likeness and pharmacokinetic properties of the prepared compounds were also evaluated. Notably, all of the novel compounds adhered to Lipinski's rule (Ro5) without any violations.http://www.sciencedirect.com/science/article/pii/S24058440240525264-Acetyl pyridineChromenesX-ray crystallographyCyclizationMolecular docking studiesAnd in silico ADMET |
| spellingShingle | Fathy M. Abdelrazek Magdi E.A. Zaki Sami A. Al-Hussain Basant Farag Ali M. Hebishy Mohamed S. Abdelfattah Safaa M. Hassan Ahmed F. El-Farargy Lyuba Iovkova David Mross Sobhi M. Gomha Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation Heliyon 4-Acetyl pyridine Chromenes X-ray crystallography Cyclization Molecular docking studies And in silico ADMET |
| title | Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation |
| title_full | Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation |
| title_fullStr | Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation |
| title_full_unstemmed | Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation |
| title_short | Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation |
| title_sort | facile one pot synthesis and in silico study of new heterocyclic scaffolds with 4 pyridyl moiety mechanistic insights and x ray crystallographic elucidation |
| topic | 4-Acetyl pyridine Chromenes X-ray crystallography Cyclization Molecular docking studies And in silico ADMET |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024052526 |
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