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The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity
Anthracycline dutomycin is a tetracyclic quinone glycoside produced by Streptomyces minoensis NRRL B-5482. SW91 is a C-12 demethylated dutomycin derivative, which was identified in our previous research. In vitro cytotoxicity and apoptosis assays of these two compounds were conducted to demonstrate...
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/PMC9144609/ https://www.ncbi.nlm.nih.gov/pubmed/35630823 http://dx.doi.org/10.3390/molecules27103348 |
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author | Xu, Ruoxuan Hu, Dinghang Lin, Jinlian Tang, Jie Zhan, Ruoting Liu, Guiyou Sun, Lei |
author_facet | Xu, Ruoxuan Hu, Dinghang Lin, Jinlian Tang, Jie Zhan, Ruoting Liu, Guiyou Sun, Lei |
author_sort | Xu, Ruoxuan |
collection | PubMed |
description | Anthracycline dutomycin is a tetracyclic quinone glycoside produced by Streptomyces minoensis NRRL B-5482. SW91 is a C-12 demethylated dutomycin derivative, which was identified in our previous research. In vitro cytotoxicity and apoptosis assays of these two compounds were conducted to demonstrate their antiproliferation activities. The results showed that both dutomycin and SW91 block cells at the S phase, whereas dutomycin shows more significant inhibition of cell growth. Their interactions with calf thymus DNA (CT-DNA) were investigated, with dutomycin exhibiting higher binding affinity. The molecular docking demonstrated that the 12-methyl group makes dutomycin attach to the groove of DNA. These findings suggest that dutomycin has binding higher affinity to DNA and impairs DNA replication resulting in more significant antitumor activity. |
format | Online Article Text |
id | pubmed-9144609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91446092022-05-29 The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity Xu, Ruoxuan Hu, Dinghang Lin, Jinlian Tang, Jie Zhan, Ruoting Liu, Guiyou Sun, Lei Molecules Article Anthracycline dutomycin is a tetracyclic quinone glycoside produced by Streptomyces minoensis NRRL B-5482. SW91 is a C-12 demethylated dutomycin derivative, which was identified in our previous research. In vitro cytotoxicity and apoptosis assays of these two compounds were conducted to demonstrate their antiproliferation activities. The results showed that both dutomycin and SW91 block cells at the S phase, whereas dutomycin shows more significant inhibition of cell growth. Their interactions with calf thymus DNA (CT-DNA) were investigated, with dutomycin exhibiting higher binding affinity. The molecular docking demonstrated that the 12-methyl group makes dutomycin attach to the groove of DNA. These findings suggest that dutomycin has binding higher affinity to DNA and impairs DNA replication resulting in more significant antitumor activity. MDPI 2022-05-23 /pmc/articles/PMC9144609/ /pubmed/35630823 http://dx.doi.org/10.3390/molecules27103348 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 Xu, Ruoxuan Hu, Dinghang Lin, Jinlian Tang, Jie Zhan, Ruoting Liu, Guiyou Sun, Lei The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity |
title | The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity |
title_full | The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity |
title_fullStr | The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity |
title_full_unstemmed | The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity |
title_short | The Critical Role of 12-Methyl Group of Anthracycline Dutomycin to Its Antiproliferative Activity |
title_sort | critical role of 12-methyl group of anthracycline dutomycin to its antiproliferative activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144609/ https://www.ncbi.nlm.nih.gov/pubmed/35630823 http://dx.doi.org/10.3390/molecules27103348 |
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