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Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies
The reaction of diaza-5H-benzo[a]phenoxazin-5-one and 5H-benzo[a]phenoxazin-5-one with various phenols catalyzed by Pd/t-BuXPhos/K(3)PO(4) system gave previously unknown ether derivatives (7a–f and 8a–f) in good yields. UV-visible, FTIR, and (1)H NMR data were used to confirm structures of the synth...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712349/ https://www.ncbi.nlm.nih.gov/pubmed/29238706 http://dx.doi.org/10.3389/fchem.2017.00107 |
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author | Ezeokonkwo, Mercy A. Ogbonna, Onyinyechi N. Okafor, Sunday N. Godwin-Nwakwasi, Evelyn U. Ibeanu, Fidelia N. Okoro, Uchechukwu C. |
author_facet | Ezeokonkwo, Mercy A. Ogbonna, Onyinyechi N. Okafor, Sunday N. Godwin-Nwakwasi, Evelyn U. Ibeanu, Fidelia N. Okoro, Uchechukwu C. |
author_sort | Ezeokonkwo, Mercy A. |
collection | PubMed |
description | The reaction of diaza-5H-benzo[a]phenoxazin-5-one and 5H-benzo[a]phenoxazin-5-one with various phenols catalyzed by Pd/t-BuXPhos/K(3)PO(4) system gave previously unknown ether derivatives (7a–f and 8a–f) in good yields. UV-visible, FTIR, and (1)H NMR data were used to confirm structures of the synthesized compounds. The parent compounds and the derivatives were screened in-silico for their drug-likeness and binding affinities to the microbial targets through molecular docking. Molinspiration software and AutoDock were used for the drug-likeness and docking studies, respectively. All the synthesized compounds showed strong drug-likeness. They also showed excellent binding affinities with glucosamine-6-phosphate synthase (2VF5), AmpC beta-lactamase (1KE4), and Lanosterol-14α-demethylase (3JUV), with compound 7e having the highest binding energies −9.5, −9.3, and −9.3 kcal/mol, respectively. These were found to be higher than the binding energies of the standard drugs. The binding energies of ciprofloxacin with 2VF5 and 1KE4 were −7.8 and −7.5 kcal/mol, respectively, while that of ketoconazole with 3JUV was −8.6 kcal/mol. The study showed that the synthesized compounds have multi-target inhibitory effects and can be very useful in multi-drug resistance cases. A 2D quantitative structural activity relationship (QSAR) model against target Glucosamine-6-phosphate synthase (2VF5) was developed using partial least squares regression (PLS) with good internal prediction (R(2) = 0.7400) and external prediction (R(2)_ predicted = 0.5475) via Molecular Operating Environment (2014). |
format | Online Article Text |
id | pubmed-5712349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57123492017-12-13 Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies Ezeokonkwo, Mercy A. Ogbonna, Onyinyechi N. Okafor, Sunday N. Godwin-Nwakwasi, Evelyn U. Ibeanu, Fidelia N. Okoro, Uchechukwu C. Front Chem Chemistry The reaction of diaza-5H-benzo[a]phenoxazin-5-one and 5H-benzo[a]phenoxazin-5-one with various phenols catalyzed by Pd/t-BuXPhos/K(3)PO(4) system gave previously unknown ether derivatives (7a–f and 8a–f) in good yields. UV-visible, FTIR, and (1)H NMR data were used to confirm structures of the synthesized compounds. The parent compounds and the derivatives were screened in-silico for their drug-likeness and binding affinities to the microbial targets through molecular docking. Molinspiration software and AutoDock were used for the drug-likeness and docking studies, respectively. All the synthesized compounds showed strong drug-likeness. They also showed excellent binding affinities with glucosamine-6-phosphate synthase (2VF5), AmpC beta-lactamase (1KE4), and Lanosterol-14α-demethylase (3JUV), with compound 7e having the highest binding energies −9.5, −9.3, and −9.3 kcal/mol, respectively. These were found to be higher than the binding energies of the standard drugs. The binding energies of ciprofloxacin with 2VF5 and 1KE4 were −7.8 and −7.5 kcal/mol, respectively, while that of ketoconazole with 3JUV was −8.6 kcal/mol. The study showed that the synthesized compounds have multi-target inhibitory effects and can be very useful in multi-drug resistance cases. A 2D quantitative structural activity relationship (QSAR) model against target Glucosamine-6-phosphate synthase (2VF5) was developed using partial least squares regression (PLS) with good internal prediction (R(2) = 0.7400) and external prediction (R(2)_ predicted = 0.5475) via Molecular Operating Environment (2014). Frontiers Media S.A. 2017-11-28 /pmc/articles/PMC5712349/ /pubmed/29238706 http://dx.doi.org/10.3389/fchem.2017.00107 Text en Copyright © 2017 Ezeokonkwo, Ogbonna, Okafor, Godwin-Nwakwasi, Ibeanu and Okoro. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Ezeokonkwo, Mercy A. Ogbonna, Onyinyechi N. Okafor, Sunday N. Godwin-Nwakwasi, Evelyn U. Ibeanu, Fidelia N. Okoro, Uchechukwu C. Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies |
title | Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies |
title_full | Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies |
title_fullStr | Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies |
title_full_unstemmed | Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies |
title_short | Angular Phenozaxine Ethers as Potent Multi-microbial Targets Inhibitors: Design, Synthesis, and Molecular Docking Studies |
title_sort | angular phenozaxine ethers as potent multi-microbial targets inhibitors: design, synthesis, and molecular docking studies |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712349/ https://www.ncbi.nlm.nih.gov/pubmed/29238706 http://dx.doi.org/10.3389/fchem.2017.00107 |
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