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Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin
An efficient and simple protocol for the synthesis of a new class of diverse bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin has been reported. A one-pot four-component condensation of 3-cyanocarbomethylindole, various aldehyde, 3-acetylindole, and ammonium acetate in glacial ace...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304590/ https://www.ncbi.nlm.nih.gov/pubmed/34299385 http://dx.doi.org/10.3390/molecules26144112 |
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author | Abo-Salem, Heba M. Abd El Salam, Hayam A. Abdel-Aziem, Anhar M. Abdel-Aziz, Mohamed S. El-Sawy, Eslam Reda |
author_facet | Abo-Salem, Heba M. Abd El Salam, Hayam A. Abdel-Aziem, Anhar M. Abdel-Aziz, Mohamed S. El-Sawy, Eslam Reda |
author_sort | Abo-Salem, Heba M. |
collection | PubMed |
description | An efficient and simple protocol for the synthesis of a new class of diverse bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin has been reported. A one-pot four-component condensation of 3-cyanocarbomethylindole, various aldehyde, 3-acetylindole, and ammonium acetate in glacial acetic acid led to the formation of 2,6-bis(1H-indol-3-yl)-4-(substituted-phenyl)pyridine-5-carbonitriles. Additionally, 2,6-bis(1H-indol-3-yl)-4-(benzofuran) pyridine-5-carbonitriles were prepared via a one-pot four-component condensation of 3-cyanocarbomethylindole, various N-substituted-indole-3-aldehydes, 2-acetylbenzofuran, and ammonium acetate. The synthesized compounds were evaluated for their ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 6538 and the Gram-negative strain Escherichia coli ATCC 25922. Some of the new compounds showed a marked selectivity against the Gram-positive and Gram-negative strains. Remarkably, five compounds 4b, 7a, 7c, 7d and 8e demonstrated good antibiofilm formation against S. aureus and E. coli. On the other hand, the release of reducing sugars and proteins from the treated bacterial strains over the untreated strains was considered to explain the disruption effect of the selected compound on the contact cells of S. aureus and E. coli. Out of all studied compounds, the binding energies and binding mode of bis-indole derivatives 7c and 7d were theoretically the best thymidylate kinase, DNA gyrase B and DNA topoisomerase IV subunit B inhibitors. |
format | Online Article Text |
id | pubmed-8304590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83045902021-07-25 Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin Abo-Salem, Heba M. Abd El Salam, Hayam A. Abdel-Aziem, Anhar M. Abdel-Aziz, Mohamed S. El-Sawy, Eslam Reda Molecules Article An efficient and simple protocol for the synthesis of a new class of diverse bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin has been reported. A one-pot four-component condensation of 3-cyanocarbomethylindole, various aldehyde, 3-acetylindole, and ammonium acetate in glacial acetic acid led to the formation of 2,6-bis(1H-indol-3-yl)-4-(substituted-phenyl)pyridine-5-carbonitriles. Additionally, 2,6-bis(1H-indol-3-yl)-4-(benzofuran) pyridine-5-carbonitriles were prepared via a one-pot four-component condensation of 3-cyanocarbomethylindole, various N-substituted-indole-3-aldehydes, 2-acetylbenzofuran, and ammonium acetate. The synthesized compounds were evaluated for their ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 6538 and the Gram-negative strain Escherichia coli ATCC 25922. Some of the new compounds showed a marked selectivity against the Gram-positive and Gram-negative strains. Remarkably, five compounds 4b, 7a, 7c, 7d and 8e demonstrated good antibiofilm formation against S. aureus and E. coli. On the other hand, the release of reducing sugars and proteins from the treated bacterial strains over the untreated strains was considered to explain the disruption effect of the selected compound on the contact cells of S. aureus and E. coli. Out of all studied compounds, the binding energies and binding mode of bis-indole derivatives 7c and 7d were theoretically the best thymidylate kinase, DNA gyrase B and DNA topoisomerase IV subunit B inhibitors. MDPI 2021-07-06 /pmc/articles/PMC8304590/ /pubmed/34299385 http://dx.doi.org/10.3390/molecules26144112 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Abo-Salem, Heba M. Abd El Salam, Hayam A. Abdel-Aziem, Anhar M. Abdel-Aziz, Mohamed S. El-Sawy, Eslam Reda Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin |
title | Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin |
title_full | Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin |
title_fullStr | Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin |
title_full_unstemmed | Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin |
title_short | Synthesis, Molecular Docking, and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin |
title_sort | synthesis, molecular docking, and biofilm formation inhibitory activity of bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304590/ https://www.ncbi.nlm.nih.gov/pubmed/34299385 http://dx.doi.org/10.3390/molecules26144112 |
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