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Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B
Human topoisomerase 1B regulates the topological state of supercoiled DNA enabling all fundamental cell processes. This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA strand and forming a transient protein–DNA covalent complex. T...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654473/ https://www.ncbi.nlm.nih.gov/pubmed/36359884 http://dx.doi.org/10.3390/cells11213486 |
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author | Ottaviani, Alessio Iacovelli, Federico Welsch, Joshua Morozzo della Rocca, Blasco Desideri, Alessandro Falconi, Mattia Calcul, Laurent Baker, Bill J. Fiorani, Paola |
author_facet | Ottaviani, Alessio Iacovelli, Federico Welsch, Joshua Morozzo della Rocca, Blasco Desideri, Alessandro Falconi, Mattia Calcul, Laurent Baker, Bill J. Fiorani, Paola |
author_sort | Ottaviani, Alessio |
collection | PubMed |
description | Human topoisomerase 1B regulates the topological state of supercoiled DNA enabling all fundamental cell processes. This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA strand and forming a transient protein–DNA covalent complex. The interaction of human topoisomerase 1B and dimethylmyricacene, a compound prepared semisynthetically from myricanol extracted from Myrica cerifera root bark, was investigated using enzymatic activity assays and molecular docking procedures. Dimethylmyricacene was shown to inhibit both the cleavage and the religation steps of the enzymatic reaction, and cell viability of A-253, FaDu, MCF-7, HeLa and HCT-116 tumor cell lines. |
format | Online Article Text |
id | pubmed-9654473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96544732022-11-15 Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B Ottaviani, Alessio Iacovelli, Federico Welsch, Joshua Morozzo della Rocca, Blasco Desideri, Alessandro Falconi, Mattia Calcul, Laurent Baker, Bill J. Fiorani, Paola Cells Article Human topoisomerase 1B regulates the topological state of supercoiled DNA enabling all fundamental cell processes. This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA strand and forming a transient protein–DNA covalent complex. The interaction of human topoisomerase 1B and dimethylmyricacene, a compound prepared semisynthetically from myricanol extracted from Myrica cerifera root bark, was investigated using enzymatic activity assays and molecular docking procedures. Dimethylmyricacene was shown to inhibit both the cleavage and the religation steps of the enzymatic reaction, and cell viability of A-253, FaDu, MCF-7, HeLa and HCT-116 tumor cell lines. MDPI 2022-11-03 /pmc/articles/PMC9654473/ /pubmed/36359884 http://dx.doi.org/10.3390/cells11213486 Text en © 2022 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 Ottaviani, Alessio Iacovelli, Federico Welsch, Joshua Morozzo della Rocca, Blasco Desideri, Alessandro Falconi, Mattia Calcul, Laurent Baker, Bill J. Fiorani, Paola Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B |
title | Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B |
title_full | Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B |
title_fullStr | Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B |
title_full_unstemmed | Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B |
title_short | Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B |
title_sort | dimethylmyricacene: an in vitro and in silico study of a semisynthetic non-camptothecin derivative compound, targeting human dna topoisomerase 1b |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654473/ https://www.ncbi.nlm.nih.gov/pubmed/36359884 http://dx.doi.org/10.3390/cells11213486 |
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