New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects

Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and CHN analysis). The...

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Main Authors: Musa A. Said, Daoud J. O. Khan, Fawzia F. Al-blewi, Nadia S. Al-Kaff, Adeeb A. Ali, Nadjet Rezki, Mohamed Reda Aouad, Mohamed Hagar
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/9/1012
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spelling doaj-5fcc4e5d0a65498cbb783bc8ecb2ebc32021-09-26T01:35:44ZengMDPI AGVaccines2076-393X2021-09-0191012101210.3390/vaccines9091012New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity AspectsMusa A. Said0Daoud J. O. Khan1Fawzia F. Al-blewi2Nadia S. Al-Kaff3Adeeb A. Ali4Nadjet Rezki5Mohamed Reda Aouad6Mohamed Hagar7Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Biology, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaChemistry Department, College of Sciences, Taibah University, Yanbu 30799, Saudi ArabiaSchiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and CHN analysis). The spectral data analysis revealed that the newly designed hydrazones exist as a mixture of <i>trans-E</i> and <i>cis</i>-<i>E</i> diastereomers. Densityfunctional theory calculations (DFT) for the Schiff bases showed that the <b><i>trans-trans</i></b> form has the lowest energy structure with maximum stability compared to the other possible geometrical isomers that could be present due to the orientation of the amidic NH–C=O group. The energy differences between the <b><i>trans</i></b>-<b><i>trans</i></b> on one side and <b><i>syn-syn</i></b> and <b><i>syn-trans</i></b> isomers on the other side were 9.26 and 5.56 kcal/mol, respectively. A quantitative structure-activity relationship investigation was also performed in terms of density functional theory. The binding affinities of the newly synthesized bases are, maybe, attributed to the presence of hydrogen bonds together with many hydrophobic interactions between the ligands and the active amino acid residue of the receptor. The superposition of the inhibitor <b>N3</b> and an example ligand into the binding pocket of 7BQY is also presented. Further interesting comparative docking analyses were performed. Quantitative structure-activity relationship calculations are presented, illustrating possible inhibitory activity. Further computer-aided cytotoxicity analysis by Drug2Way and PASS online software was carried out for Schiff base ligands against various cancer cell lines. Overall, the results of this study suggest that these Schiff base derivatives may be considered for further investigation as possible therapeutic agents for COVID-19.https://www.mdpi.com/2076-393X/9/9/10121,2,3-triazoleSchiff base (SB)DFT-QSARCOVID-19molecular dockingcytotoxicity
collection DOAJ
language English
format Article
sources DOAJ
author Musa A. Said
Daoud J. O. Khan
Fawzia F. Al-blewi
Nadia S. Al-Kaff
Adeeb A. Ali
Nadjet Rezki
Mohamed Reda Aouad
Mohamed Hagar
spellingShingle Musa A. Said
Daoud J. O. Khan
Fawzia F. Al-blewi
Nadia S. Al-Kaff
Adeeb A. Ali
Nadjet Rezki
Mohamed Reda Aouad
Mohamed Hagar
New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects
Vaccines
1,2,3-triazole
Schiff base (SB)
DFT-QSAR
COVID-19
molecular docking
cytotoxicity
author_facet Musa A. Said
Daoud J. O. Khan
Fawzia F. Al-blewi
Nadia S. Al-Kaff
Adeeb A. Ali
Nadjet Rezki
Mohamed Reda Aouad
Mohamed Hagar
author_sort Musa A. Said
title New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects
title_short New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects
title_full New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects
title_fullStr New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects
title_full_unstemmed New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects
title_sort new 1,2,3-triazole scaffold schiff bases as potential anti-covid-19: design, synthesis, dft-molecular docking, and cytotoxicity aspects
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2021-09-01
description Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and CHN analysis). The spectral data analysis revealed that the newly designed hydrazones exist as a mixture of <i>trans-E</i> and <i>cis</i>-<i>E</i> diastereomers. Densityfunctional theory calculations (DFT) for the Schiff bases showed that the <b><i>trans-trans</i></b> form has the lowest energy structure with maximum stability compared to the other possible geometrical isomers that could be present due to the orientation of the amidic NH–C=O group. The energy differences between the <b><i>trans</i></b>-<b><i>trans</i></b> on one side and <b><i>syn-syn</i></b> and <b><i>syn-trans</i></b> isomers on the other side were 9.26 and 5.56 kcal/mol, respectively. A quantitative structure-activity relationship investigation was also performed in terms of density functional theory. The binding affinities of the newly synthesized bases are, maybe, attributed to the presence of hydrogen bonds together with many hydrophobic interactions between the ligands and the active amino acid residue of the receptor. The superposition of the inhibitor <b>N3</b> and an example ligand into the binding pocket of 7BQY is also presented. Further interesting comparative docking analyses were performed. Quantitative structure-activity relationship calculations are presented, illustrating possible inhibitory activity. Further computer-aided cytotoxicity analysis by Drug2Way and PASS online software was carried out for Schiff base ligands against various cancer cell lines. Overall, the results of this study suggest that these Schiff base derivatives may be considered for further investigation as possible therapeutic agents for COVID-19.
topic 1,2,3-triazole
Schiff base (SB)
DFT-QSAR
COVID-19
molecular docking
cytotoxicity
url https://www.mdpi.com/2076-393X/9/9/1012
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