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Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures

BACKGROUND: Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt(2)). The...

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Autores principales: Barakat, Assem, Al-Majid, Abdullah M., Al-Qahtany, Bander M., Ali, M., Teleb, Mohamed, Al-Agamy, Mohamed H., Naz, Sehrish, Ul-Haq, Zaheer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852137/
https://www.ncbi.nlm.nih.gov/pubmed/29541952
http://dx.doi.org/10.1186/s13065-018-0399-0
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author Barakat, Assem
Al-Majid, Abdullah M.
Al-Qahtany, Bander M.
Ali, M.
Teleb, Mohamed
Al-Agamy, Mohamed H.
Naz, Sehrish
Ul-Haq, Zaheer
author_facet Barakat, Assem
Al-Majid, Abdullah M.
Al-Qahtany, Bander M.
Ali, M.
Teleb, Mohamed
Al-Agamy, Mohamed H.
Naz, Sehrish
Ul-Haq, Zaheer
author_sort Barakat, Assem
collection PubMed
description BACKGROUND: Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt(2)). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques ((1)H-NMR, (13)C-NMR, IR, MS, and CHN). RESULTS: The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L. CONCLUSION: In-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13065-018-0399-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-58521372018-03-21 Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures Barakat, Assem Al-Majid, Abdullah M. Al-Qahtany, Bander M. Ali, M. Teleb, Mohamed Al-Agamy, Mohamed H. Naz, Sehrish Ul-Haq, Zaheer Chem Cent J Research Article BACKGROUND: Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt(2)). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques ((1)H-NMR, (13)C-NMR, IR, MS, and CHN). RESULTS: The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L. CONCLUSION: In-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13065-018-0399-0) contains supplementary material, which is available to authorized users. Springer International Publishing 2018-03-14 /pmc/articles/PMC5852137/ /pubmed/29541952 http://dx.doi.org/10.1186/s13065-018-0399-0 Text en © The Author(s) 2018 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
Barakat, Assem
Al-Majid, Abdullah M.
Al-Qahtany, Bander M.
Ali, M.
Teleb, Mohamed
Al-Agamy, Mohamed H.
Naz, Sehrish
Ul-Haq, Zaheer
Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures
title Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures
title_full Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures
title_fullStr Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures
title_full_unstemmed Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures
title_short Synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures
title_sort synthesis, antimicrobial activity, pharmacophore modeling and molecular docking studies of new pyrazole-dimedone hybrid architectures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852137/
https://www.ncbi.nlm.nih.gov/pubmed/29541952
http://dx.doi.org/10.1186/s13065-018-0399-0
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