Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , |
Tipo de documento: | preprint |
Idioma: | por |
Título da fonte: | SciELO Preprints |
Texto Completo: | https://preprints.scielo.org/index.php/scielo/preprint/view/6188 |
Resumo: | Computer-aided drug planning strategies have contributed to the research and development of new anti-tuberculosis (TB) drugs to avoid resistance and reduce treatment time and the number of drugs used in therapy. The aim of work was to carry out a docking study to identify the possible mechanism of action of the hits LabMol73, 84, 86 and 93 previously tested in the Microplate Assay Blue Alamar (MABA), Low Oxygen Recovery Assay (LORA) assays in sensitive strains from M.tb. H37Rv and resistant to the standard drugs rifampicin and isoniazid, due to the promising inhibitory result against these strains, suggesting a different mechanism of action from existing drugs. The reverse virtual screening was performed on the Pharmmapper platform, which identifies targets by pharmacophoric model. The most promising targets have been validated. The DM was performed in the OpenEye Maestro program for analysis of poses and energy score. Sixteen targets M.tb. H37Rv were identified and only nine demonstrated viability for computational testing. The most promising results were observed in the mycolic acid cyclopropane synthase (PDB:1L1E) and pantothenate synthetase (PDB:1N2B) targets. Since, in the target 1L1E score results obtained were between -6.998 to -7.767 kcal/mol. In the 1N2B target the results were between -6.421 to -7.293 kcal/mol, presenting themselves as the most promising targets due to their similar score scores between the two targets suggesting that the mechanism of action may be the inhibition of one of these targets. These targets proved to be promising for elucidating the mechanism of action of the analyzed nitro heteroaryl chalcones, as they corroborate the assay against resistant strains, demonstrating that standard drugs have activity against other targets and also because mycolic acid and pantothenate are directly linked to virulence and resistance of M.tb. H37Rv. |
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Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activityTarget fishing e modelagem molecular de nitroheteroarilchalconas com potente atividade antituberculoseNitroheteroaryl chalconesTarget fishingTuberculoseNitroheteroaryl chalconesTarget fishingTuberculosisComputer-aided drug planning strategies have contributed to the research and development of new anti-tuberculosis (TB) drugs to avoid resistance and reduce treatment time and the number of drugs used in therapy. The aim of work was to carry out a docking study to identify the possible mechanism of action of the hits LabMol73, 84, 86 and 93 previously tested in the Microplate Assay Blue Alamar (MABA), Low Oxygen Recovery Assay (LORA) assays in sensitive strains from M.tb. H37Rv and resistant to the standard drugs rifampicin and isoniazid, due to the promising inhibitory result against these strains, suggesting a different mechanism of action from existing drugs. The reverse virtual screening was performed on the Pharmmapper platform, which identifies targets by pharmacophoric model. The most promising targets have been validated. The DM was performed in the OpenEye Maestro program for analysis of poses and energy score. Sixteen targets M.tb. H37Rv were identified and only nine demonstrated viability for computational testing. The most promising results were observed in the mycolic acid cyclopropane synthase (PDB:1L1E) and pantothenate synthetase (PDB:1N2B) targets. Since, in the target 1L1E score results obtained were between -6.998 to -7.767 kcal/mol. In the 1N2B target the results were between -6.421 to -7.293 kcal/mol, presenting themselves as the most promising targets due to their similar score scores between the two targets suggesting that the mechanism of action may be the inhibition of one of these targets. These targets proved to be promising for elucidating the mechanism of action of the analyzed nitro heteroaryl chalcones, as they corroborate the assay against resistant strains, demonstrating that standard drugs have activity against other targets and also because mycolic acid and pantothenate are directly linked to virulence and resistance of M.tb. H37Rv.Computer-aided drug planning strategies have contributed to the research and development of new anti-tuberculosis (TB) drugs to avoid resistance and reduce treatment time and the number of drugs used in therapy. The aim of work was to carry out a docking study to identify the possible mechanism of action of the hits LabMol73, 84, 86 and 93 previously tested in the Microplate Assay Blue Alamar (MABA), Low Oxygen Recovery Assay (LORA) assays in sensitive strains from M.tb. H37Rv and resistant to the standard drugs rifampicin and isoniazid, due to the promising inhibitory result against these strains, suggesting a different mechanism of action from existing drugs. The reverse virtual screening was performed on the Pharmmapper platform, which identifies targets by pharmacophoric model. The most promising targets have been validated. The DM was performed in the OpenEye Maestro program for analysis of poses and energy score. Sixteen targets M.tb. H37Rv were identified and only nine demonstrated viability for computational testing. The most promising results were observed in the mycolic acid cyclopropane synthase (PDB:1L1E) and pantothenate synthetase (PDB:1N2B) targets. Since, in the target 1L1E score results obtained were between -6.998 to -7.767 kcal/mol. In the 1N2B target the results were between -6.421 to -7.293 kcal/mol, presenting themselves as the most promising targets due to their similar score scores between the two targets suggesting that the mechanism of action may be the inhibition of one of these targets. These targets proved to be promising for elucidating the mechanism of action of the analyzed nitro heteroaryl chalcones, as they corroborate the assay against resistant strains, demonstrating that standard drugs have activity against other targets and also because mycolic acid and pantothenate are directly linked to virulence and resistance of M.tb. H37Rv.SciELO PreprintsSciELO PreprintsSciELO Preprints2023-06-06info:eu-repo/semantics/preprintinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://preprints.scielo.org/index.php/scielo/preprint/view/618810.1590/SciELOPreprints.6188porhttps://preprints.scielo.org/index.php/scielo/article/view/6188/11863Copyright (c) 2023 Marcelo do Nascimento Gomes, Graziela Fernanda Sousa, Rafael Junio Souza, Bruce Soares Cardosohttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessGomes, Marcelo do NascimentoSousa, Graziela FernandaSouza, Rafael JunioCardoso, Bruce Soaresreponame:SciELO Preprintsinstname:Scientific Electronic Library Online (SCIELO)instacron:SCI2023-06-02T19:30:35Zoai:ops.preprints.scielo.org:preprint/6188Servidor de preprintshttps://preprints.scielo.org/index.php/scieloONGhttps://preprints.scielo.org/index.php/scielo/oaiscielo.submission@scielo.orgopendoar:2023-06-02T19:30:35SciELO Preprints - Scientific Electronic Library Online (SCIELO)false |
dc.title.none.fl_str_mv |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity Target fishing e modelagem molecular de nitroheteroarilchalconas com potente atividade antituberculose |
title |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity |
spellingShingle |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity Gomes, Marcelo do Nascimento Nitroheteroaryl chalcones Target fishing Tuberculose Nitroheteroaryl chalcones Target fishing Tuberculosis |
title_short |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity |
title_full |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity |
title_fullStr |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity |
title_full_unstemmed |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity |
title_sort |
Target fishing and molecular modeling of nitroheteroaylchalcones with potent antituberculosis activity |
author |
Gomes, Marcelo do Nascimento |
author_facet |
Gomes, Marcelo do Nascimento Sousa, Graziela Fernanda Souza, Rafael Junio Cardoso, Bruce Soares |
author_role |
author |
author2 |
Sousa, Graziela Fernanda Souza, Rafael Junio Cardoso, Bruce Soares |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Gomes, Marcelo do Nascimento Sousa, Graziela Fernanda Souza, Rafael Junio Cardoso, Bruce Soares |
dc.subject.por.fl_str_mv |
Nitroheteroaryl chalcones Target fishing Tuberculose Nitroheteroaryl chalcones Target fishing Tuberculosis |
topic |
Nitroheteroaryl chalcones Target fishing Tuberculose Nitroheteroaryl chalcones Target fishing Tuberculosis |
description |
Computer-aided drug planning strategies have contributed to the research and development of new anti-tuberculosis (TB) drugs to avoid resistance and reduce treatment time and the number of drugs used in therapy. The aim of work was to carry out a docking study to identify the possible mechanism of action of the hits LabMol73, 84, 86 and 93 previously tested in the Microplate Assay Blue Alamar (MABA), Low Oxygen Recovery Assay (LORA) assays in sensitive strains from M.tb. H37Rv and resistant to the standard drugs rifampicin and isoniazid, due to the promising inhibitory result against these strains, suggesting a different mechanism of action from existing drugs. The reverse virtual screening was performed on the Pharmmapper platform, which identifies targets by pharmacophoric model. The most promising targets have been validated. The DM was performed in the OpenEye Maestro program for analysis of poses and energy score. Sixteen targets M.tb. H37Rv were identified and only nine demonstrated viability for computational testing. The most promising results were observed in the mycolic acid cyclopropane synthase (PDB:1L1E) and pantothenate synthetase (PDB:1N2B) targets. Since, in the target 1L1E score results obtained were between -6.998 to -7.767 kcal/mol. In the 1N2B target the results were between -6.421 to -7.293 kcal/mol, presenting themselves as the most promising targets due to their similar score scores between the two targets suggesting that the mechanism of action may be the inhibition of one of these targets. These targets proved to be promising for elucidating the mechanism of action of the analyzed nitro heteroaryl chalcones, as they corroborate the assay against resistant strains, demonstrating that standard drugs have activity against other targets and also because mycolic acid and pantothenate are directly linked to virulence and resistance of M.tb. H37Rv. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-06-06 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/preprint info:eu-repo/semantics/publishedVersion |
format |
preprint |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://preprints.scielo.org/index.php/scielo/preprint/view/6188 10.1590/SciELOPreprints.6188 |
url |
https://preprints.scielo.org/index.php/scielo/preprint/view/6188 |
identifier_str_mv |
10.1590/SciELOPreprints.6188 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://preprints.scielo.org/index.php/scielo/article/view/6188/11863 |
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https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
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https://creativecommons.org/licenses/by/4.0 |
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openAccess |
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application/pdf |
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SciELO Preprints SciELO Preprints SciELO Preprints |
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SciELO Preprints SciELO Preprints SciELO Preprints |
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SciELO Preprints - Scientific Electronic Library Online (SCIELO) |
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