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Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents
In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membere...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801890/ https://www.ncbi.nlm.nih.gov/pubmed/35111810 http://dx.doi.org/10.3389/fmolb.2021.775013 |
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author | Hassan, Entesar A. Shehadi, Ihsan A. Elmaghraby, Awatef M. Mostafa, Hadir M. Zayed, Salem E. Abdelmonsef, Aboubakr H. |
author_facet | Hassan, Entesar A. Shehadi, Ihsan A. Elmaghraby, Awatef M. Mostafa, Hadir M. Zayed, Salem E. Abdelmonsef, Aboubakr H. |
author_sort | Hassan, Entesar A. |
collection | PubMed |
description | In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent. |
format | Online Article Text |
id | pubmed-8801890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88018902022-02-01 Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents Hassan, Entesar A. Shehadi, Ihsan A. Elmaghraby, Awatef M. Mostafa, Hadir M. Zayed, Salem E. Abdelmonsef, Aboubakr H. Front Mol Biosci Molecular Biosciences In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent. Frontiers Media S.A. 2022-01-17 /pmc/articles/PMC8801890/ /pubmed/35111810 http://dx.doi.org/10.3389/fmolb.2021.775013 Text en Copyright © 2022 Hassan, Shehadi, Elmaghraby, Mostafa, Zayed and Abdelmonsef. https://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) and the copyright owner(s) 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 | Molecular Biosciences Hassan, Entesar A. Shehadi, Ihsan A. Elmaghraby, Awatef M. Mostafa, Hadir M. Zayed, Salem E. Abdelmonsef, Aboubakr H. Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents |
title | Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents |
title_full | Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents |
title_fullStr | Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents |
title_full_unstemmed | Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents |
title_short | Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents |
title_sort | synthesis, molecular docking analysis and in vitro biological evaluation of some new heterocyclic scaffolds-based indole moiety as possible antimicrobial agents |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801890/ https://www.ncbi.nlm.nih.gov/pubmed/35111810 http://dx.doi.org/10.3389/fmolb.2021.775013 |
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