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Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids
[Image: see text] A series of new heterocycle hybrids incorporating pyrazole and isoxazoline rings was successfully synthesized, characterized, and evaluated for their antimicrobial responses. The synthesized compounds were obtained utilizing N-alkylation and 1,3-dipolar cycloaddition reactions, as...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773794/ https://www.ncbi.nlm.nih.gov/pubmed/36570248 http://dx.doi.org/10.1021/acsomega.2c05788 |
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author | Chalkha, Mohammed Nour, Hassan Chebbac, Khalid Nakkabi, Asmae Bahsis, Lahoucine Bakhouch, Mohamed Akhazzane, Mohamed Bourass, Mohamed Chtita, Samir Bin Jardan, Yousef A. Augustyniak, Maria Bourhia, Mohammed Aboul-Soud, Mourad A.M. El Yazidi, Mohamed |
author_facet | Chalkha, Mohammed Nour, Hassan Chebbac, Khalid Nakkabi, Asmae Bahsis, Lahoucine Bakhouch, Mohamed Akhazzane, Mohamed Bourass, Mohamed Chtita, Samir Bin Jardan, Yousef A. Augustyniak, Maria Bourhia, Mohammed Aboul-Soud, Mourad A.M. El Yazidi, Mohamed |
author_sort | Chalkha, Mohammed |
collection | PubMed |
description | [Image: see text] A series of new heterocycle hybrids incorporating pyrazole and isoxazoline rings was successfully synthesized, characterized, and evaluated for their antimicrobial responses. The synthesized compounds were obtained utilizing N-alkylation and 1,3-dipolar cycloaddition reactions, as well as their structures were established through spectroscopic methods and confirmed by mass spectrometry. To get more light on the regioselective synthesis of new hybrid compounds, mechanistic studies were performed using DFT calculations with B3LYP/6-31G(d,p) basis set. Additionally, the results of the preliminary screening indicate that some of the examined hybrids showed potent antimicrobial activity, compared to standard drugs. The results confirm that the antimicrobial activity is strongly dependent on the nature of the substituents linked pyrazole and isoxazoline rings. Furthermore, molecular docking studies were conducted to highlight the interaction modes between the investigated hybrid compounds and the Escherichia coli and Candida albicans receptors. Notably, the results demonstrate that the investigated compounds have strong protein binding affinities. The stability of the formed complexes by the binding between the hybrid compound 6c, and the target proteins was also confirmed using a 100 ns molecular dynamics simulation. Finally, the prediction of ADMET properties suggests that almost all hybrid compounds possess good pharmacokinetic profiles and no signs of observed toxicity, except for compounds 6e, 6f, and 6g. |
format | Online Article Text |
id | pubmed-9773794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-97737942022-12-23 Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids Chalkha, Mohammed Nour, Hassan Chebbac, Khalid Nakkabi, Asmae Bahsis, Lahoucine Bakhouch, Mohamed Akhazzane, Mohamed Bourass, Mohamed Chtita, Samir Bin Jardan, Yousef A. Augustyniak, Maria Bourhia, Mohammed Aboul-Soud, Mourad A.M. El Yazidi, Mohamed ACS Omega [Image: see text] A series of new heterocycle hybrids incorporating pyrazole and isoxazoline rings was successfully synthesized, characterized, and evaluated for their antimicrobial responses. The synthesized compounds were obtained utilizing N-alkylation and 1,3-dipolar cycloaddition reactions, as well as their structures were established through spectroscopic methods and confirmed by mass spectrometry. To get more light on the regioselective synthesis of new hybrid compounds, mechanistic studies were performed using DFT calculations with B3LYP/6-31G(d,p) basis set. Additionally, the results of the preliminary screening indicate that some of the examined hybrids showed potent antimicrobial activity, compared to standard drugs. The results confirm that the antimicrobial activity is strongly dependent on the nature of the substituents linked pyrazole and isoxazoline rings. Furthermore, molecular docking studies were conducted to highlight the interaction modes between the investigated hybrid compounds and the Escherichia coli and Candida albicans receptors. Notably, the results demonstrate that the investigated compounds have strong protein binding affinities. The stability of the formed complexes by the binding between the hybrid compound 6c, and the target proteins was also confirmed using a 100 ns molecular dynamics simulation. Finally, the prediction of ADMET properties suggests that almost all hybrid compounds possess good pharmacokinetic profiles and no signs of observed toxicity, except for compounds 6e, 6f, and 6g. American Chemical Society 2022-12-08 /pmc/articles/PMC9773794/ /pubmed/36570248 http://dx.doi.org/10.1021/acsomega.2c05788 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Chalkha, Mohammed Nour, Hassan Chebbac, Khalid Nakkabi, Asmae Bahsis, Lahoucine Bakhouch, Mohamed Akhazzane, Mohamed Bourass, Mohamed Chtita, Samir Bin Jardan, Yousef A. Augustyniak, Maria Bourhia, Mohammed Aboul-Soud, Mourad A.M. El Yazidi, Mohamed Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids |
title | Synthesis, Characterization,
DFT Mechanistic Study,
Antimicrobial Activity, Molecular Modeling, and ADMET Properties of
Novel Pyrazole-isoxazoline Hybrids |
title_full | Synthesis, Characterization,
DFT Mechanistic Study,
Antimicrobial Activity, Molecular Modeling, and ADMET Properties of
Novel Pyrazole-isoxazoline Hybrids |
title_fullStr | Synthesis, Characterization,
DFT Mechanistic Study,
Antimicrobial Activity, Molecular Modeling, and ADMET Properties of
Novel Pyrazole-isoxazoline Hybrids |
title_full_unstemmed | Synthesis, Characterization,
DFT Mechanistic Study,
Antimicrobial Activity, Molecular Modeling, and ADMET Properties of
Novel Pyrazole-isoxazoline Hybrids |
title_short | Synthesis, Characterization,
DFT Mechanistic Study,
Antimicrobial Activity, Molecular Modeling, and ADMET Properties of
Novel Pyrazole-isoxazoline Hybrids |
title_sort | synthesis, characterization,
dft mechanistic study,
antimicrobial activity, molecular modeling, and admet properties of
novel pyrazole-isoxazoline hybrids |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773794/ https://www.ncbi.nlm.nih.gov/pubmed/36570248 http://dx.doi.org/10.1021/acsomega.2c05788 |
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