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Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety
BACKGROUND: A series of novel N-(2, 6-dimethoxypyrimidin-4-yl)-4-(3-(aryl)thioureido) benzenesulfonamides 3a–t was synthesized by the addition of N-(2,6-dimethoxypyrimidin-4-yl)-4-isothiocyanatobenzenesulfonamide 2 to the appropriate aromatic amine. The structures of the synthesized compounds were i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438335/ https://www.ncbi.nlm.nih.gov/pubmed/29086825 http://dx.doi.org/10.1186/s13065-017-0271-7 |
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author | Ghorab, Mostafa M. El-Gaby, Mohamed S. A. Soliman, Aiten M. Alsaid, Mansour S. Abdel-Aziz, Marwa M. Elaasser, Mahmoud M. |
author_facet | Ghorab, Mostafa M. El-Gaby, Mohamed S. A. Soliman, Aiten M. Alsaid, Mansour S. Abdel-Aziz, Marwa M. Elaasser, Mahmoud M. |
author_sort | Ghorab, Mostafa M. |
collection | PubMed |
description | BACKGROUND: A series of novel N-(2, 6-dimethoxypyrimidin-4-yl)-4-(3-(aryl)thioureido) benzenesulfonamides 3a–t was synthesized by the addition of N-(2,6-dimethoxypyrimidin-4-yl)-4-isothiocyanatobenzenesulfonamide 2 to the appropriate aromatic amine. The structures of the synthesized compounds were inspired from the second line antituberculosis pro-drugs. RESULTS: Most of the new compounds were screened for their activity against Mycobacterium tuberculosis. The results of the antimycobacterial assay showed that compound 3i exerted the highest activity (MIC = 3.13 µg/mL), followed by compound 3s (MIC = 6.25 µg/mL). CONCLUSION: The structure–activity relationship (SAR) analysis revealed that the introduction of the benzo[1,3]dioxol moiety in 3i and the 4-morpholinyl-4-phenyl moiety in 3s has proven to give the most potent compounds in this study. Docking of the promising compounds inside the active site of M. tuberculosis enoyl reductase InhA was performed in order to emphasize the results. The compounds showed a similar orientation to that of GSK 625 inside the active site of 5JFO and bind to Met 98 in a way similar to that of the co-crystallized ligand. |
format | Online Article Text |
id | pubmed-5438335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-54383352017-06-06 Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety Ghorab, Mostafa M. El-Gaby, Mohamed S. A. Soliman, Aiten M. Alsaid, Mansour S. Abdel-Aziz, Marwa M. Elaasser, Mahmoud M. Chem Cent J Research Article BACKGROUND: A series of novel N-(2, 6-dimethoxypyrimidin-4-yl)-4-(3-(aryl)thioureido) benzenesulfonamides 3a–t was synthesized by the addition of N-(2,6-dimethoxypyrimidin-4-yl)-4-isothiocyanatobenzenesulfonamide 2 to the appropriate aromatic amine. The structures of the synthesized compounds were inspired from the second line antituberculosis pro-drugs. RESULTS: Most of the new compounds were screened for their activity against Mycobacterium tuberculosis. The results of the antimycobacterial assay showed that compound 3i exerted the highest activity (MIC = 3.13 µg/mL), followed by compound 3s (MIC = 6.25 µg/mL). CONCLUSION: The structure–activity relationship (SAR) analysis revealed that the introduction of the benzo[1,3]dioxol moiety in 3i and the 4-morpholinyl-4-phenyl moiety in 3s has proven to give the most potent compounds in this study. Docking of the promising compounds inside the active site of M. tuberculosis enoyl reductase InhA was performed in order to emphasize the results. The compounds showed a similar orientation to that of GSK 625 inside the active site of 5JFO and bind to Met 98 in a way similar to that of the co-crystallized ligand. Springer International Publishing 2017-05-19 /pmc/articles/PMC5438335/ /pubmed/29086825 http://dx.doi.org/10.1186/s13065-017-0271-7 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Ghorab, Mostafa M. El-Gaby, Mohamed S. A. Soliman, Aiten M. Alsaid, Mansour S. Abdel-Aziz, Marwa M. Elaasser, Mahmoud M. Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
title | Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
title_full | Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
title_fullStr | Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
title_full_unstemmed | Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
title_short | Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
title_sort | synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438335/ https://www.ncbi.nlm.nih.gov/pubmed/29086825 http://dx.doi.org/10.1186/s13065-017-0271-7 |
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