Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety
Abstract 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 compound...
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doaj-d8d0c62b6de2422dbe7556b08c48bf662021-08-02T11:16:43ZengBMCChemistry Central Journal1752-153X2017-05-0111111210.1186/s13065-017-0271-7Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moietyMostafa M. Ghorab0Mohamed S. A. El-Gaby1Aiten M. Soliman2Mansour S. Alsaid3Marwa M. Abdel-Aziz4Mahmoud M. Elaasser5Department of Pharmacognosy, College of Pharmacy, King Saud UniversityDepartment of Chemistry, Faculty of Science, Al-Azhar UniversityDepartment of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy AuthorityDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityThe Regional Center for Mycology and Biotechnology, Al-Azhar UniversityThe Regional Center for Mycology and Biotechnology, Al-Azhar UniversityAbstract 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.http://link.springer.com/article/10.1186/s13065-017-0271-7ThioureaSulfonamidesStructure–activity relationshipAntimycobacterial |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mostafa M. Ghorab Mohamed S. A. El-Gaby Aiten M. Soliman Mansour S. Alsaid Marwa M. Abdel-Aziz Mahmoud M. Elaasser |
spellingShingle |
Mostafa M. Ghorab Mohamed S. A. El-Gaby Aiten M. Soliman Mansour S. Alsaid Marwa M. Abdel-Aziz Mahmoud M. Elaasser Synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety Chemistry Central Journal Thiourea Sulfonamides Structure–activity relationship Antimycobacterial |
author_facet |
Mostafa M. Ghorab Mohamed S. A. El-Gaby Aiten M. Soliman Mansour S. Alsaid Marwa M. Abdel-Aziz Mahmoud M. Elaasser |
author_sort |
Mostafa M. Ghorab |
title |
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_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_sort |
synthesis, docking study and biological evaluation of some new thiourea derivatives bearing benzenesulfonamide moiety |
publisher |
BMC |
series |
Chemistry Central Journal |
issn |
1752-153X |
publishDate |
2017-05-01 |
description |
Abstract 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. |
topic |
Thiourea Sulfonamides Structure–activity relationship Antimycobacterial |
url |
http://link.springer.com/article/10.1186/s13065-017-0271-7 |
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