A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity

Type II DNA topoisomerase (topo II) is an essential nuclear enzyme and a well-validated anticancer drug target. Previously, we have carried out several rounds of structural optimizations on our in-house topo II inhibitor <b>E17</b>, which was shown to have superior anticancer activity an...

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Autores principales:	Zhi-Ying Li, Guang-Sen Xu, Xun Li
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	acridone derivative 6h topo II inhibitor DNA intercalating agent chemotherapy less cardiotoxicity Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e86a3e708ab4408d953393fc9792cecd
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spelling	oai:doaj.org-article:e86a3e708ab4408d953393fc9792cecd2021-11-25T17:11:52ZA Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity10.3390/cells101131382073-4409https://doaj.org/article/e86a3e708ab4408d953393fc9792cecd2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3138https://doaj.org/toc/2073-4409Type II DNA topoisomerase (topo II) is an essential nuclear enzyme and a well-validated anticancer drug target. Previously, we have carried out several rounds of structural optimizations on our in-house topo II inhibitor <b>E17</b>, which was shown to have superior anticancer activity and less risk of multidrug resistance (MDR). Among the newly developed acridone derivatives, 6h displayed significant anticancer efficacy with unique mechanisms of action. At low concentrations, it arrested cancer cell cycles and triggered cell apoptosis, which is similar to the action of the well-known topo II inhibitor VP16. By contrast, 6h showed significant and long-term anti-proliferative activity at relatively high concentrations, with negligible influence on apoptosis. In addition, 6h exhibited no serious cardiotoxicity compared to doxorubicin (DOXO), a widely used topo II-targeting antineoplastic drug in clinic, but with damaging myocardial side effects. Collectively, our present work has supported the therapeutic value of 6h as a promising chemotherapy for cancers.Zhi-Ying LiGuang-Sen XuXun LiMDPI AGarticleacridone derivative 6htopo II inhibitorDNA intercalating agentchemotherapyless cardiotoxicityBiology (General)QH301-705.5ENCells, Vol 10, Iss 3138, p 3138 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acridone derivative 6h topo II inhibitor DNA intercalating agent chemotherapy less cardiotoxicity Biology (General) QH301-705.5
spellingShingle	acridone derivative 6h topo II inhibitor DNA intercalating agent chemotherapy less cardiotoxicity Biology (General) QH301-705.5 Zhi-Ying Li Guang-Sen Xu Xun Li A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity
description	Type II DNA topoisomerase (topo II) is an essential nuclear enzyme and a well-validated anticancer drug target. Previously, we have carried out several rounds of structural optimizations on our in-house topo II inhibitor <b>E17</b>, which was shown to have superior anticancer activity and less risk of multidrug resistance (MDR). Among the newly developed acridone derivatives, 6h displayed significant anticancer efficacy with unique mechanisms of action. At low concentrations, it arrested cancer cell cycles and triggered cell apoptosis, which is similar to the action of the well-known topo II inhibitor VP16. By contrast, 6h showed significant and long-term anti-proliferative activity at relatively high concentrations, with negligible influence on apoptosis. In addition, 6h exhibited no serious cardiotoxicity compared to doxorubicin (DOXO), a widely used topo II-targeting antineoplastic drug in clinic, but with damaging myocardial side effects. Collectively, our present work has supported the therapeutic value of 6h as a promising chemotherapy for cancers.
format	article
author	Zhi-Ying Li Guang-Sen Xu Xun Li
author_facet	Zhi-Ying Li Guang-Sen Xu Xun Li
author_sort	Zhi-Ying Li
title	A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity
title_short	A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity
title_full	A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity
title_fullStr	A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity
title_full_unstemmed	A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity
title_sort	unique topoisomerase ii inhibitor with dose-affected anticancer mechanisms and less cardiotoxicity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e86a3e708ab4408d953393fc9792cecd
work_keys_str_mv	AT zhiyingli auniquetopoisomeraseiiinhibitorwithdoseaffectedanticancermechanismsandlesscardiotoxicity AT guangsenxu auniquetopoisomeraseiiinhibitorwithdoseaffectedanticancermechanismsandlesscardiotoxicity AT xunli auniquetopoisomeraseiiinhibitorwithdoseaffectedanticancermechanismsandlesscardiotoxicity AT zhiyingli uniquetopoisomeraseiiinhibitorwithdoseaffectedanticancermechanismsandlesscardiotoxicity AT guangsenxu uniquetopoisomeraseiiinhibitorwithdoseaffectedanticancermechanismsandlesscardiotoxicity AT xunli uniquetopoisomeraseiiinhibitorwithdoseaffectedanticancermechanismsandlesscardiotoxicity
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A Unique Topoisomerase II Inhibitor with Dose-Affected Anticancer Mechanisms and Less Cardiotoxicity

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