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1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals

Arsenicals have been widely used in the treatment of cancers such as leukemia and other tumors. However, their side effects limit their clinical application. Stiripentol, a second-line adjunctive treatment for epilepsy with a good safety profile, inhibits microsomal cytochrome-P450-family enzymes to...

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Autores principales: Shi, Xue-Min, She, Wen-Yan, Liu, Ting-Ting, Gao, Lian-Xun, Liu, Yu-Jiao, Liu, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266561/
https://www.ncbi.nlm.nih.gov/pubmed/35805931
http://dx.doi.org/10.3390/ijms23136930
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author Shi, Xue-Min
She, Wen-Yan
Liu, Ting-Ting
Gao, Lian-Xun
Liu, Yu-Jiao
Liu, Yi
author_facet Shi, Xue-Min
She, Wen-Yan
Liu, Ting-Ting
Gao, Lian-Xun
Liu, Yu-Jiao
Liu, Yi
author_sort Shi, Xue-Min
collection PubMed
description Arsenicals have been widely used in the treatment of cancers such as leukemia and other tumors. However, their side effects limit their clinical application. Stiripentol, a second-line adjunctive treatment for epilepsy with a good safety profile, inhibits microsomal cytochrome-P450-family enzymes to extend the retention time of co-administration. Inspired by the metabolism of stiripentol, the 1,3-benzodioxole responsible for the inhibition and its metabolic derivatives were conjugated with arsenical precursors. The fabricated arsenicals were eliminated much slower in mice and maintained an efficient concentration in the blood for a longer time than that of the arsenical precursors. They also performed better in anti-proliferation by inhibiting the thioredoxin system to induce oxidative stress, and concomitantly to initiate apoptosis in vitro and in vivo. The fabricated arsenicals reversed the hemogram of tumor-bearing mice to normal and eliminated the tumor without causing damage to any organs, exhibiting a good design strategy and pre-clinical application for leukemia and other tumors.
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spelling pubmed-92665612022-07-09 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals Shi, Xue-Min She, Wen-Yan Liu, Ting-Ting Gao, Lian-Xun Liu, Yu-Jiao Liu, Yi Int J Mol Sci Article Arsenicals have been widely used in the treatment of cancers such as leukemia and other tumors. However, their side effects limit their clinical application. Stiripentol, a second-line adjunctive treatment for epilepsy with a good safety profile, inhibits microsomal cytochrome-P450-family enzymes to extend the retention time of co-administration. Inspired by the metabolism of stiripentol, the 1,3-benzodioxole responsible for the inhibition and its metabolic derivatives were conjugated with arsenical precursors. The fabricated arsenicals were eliminated much slower in mice and maintained an efficient concentration in the blood for a longer time than that of the arsenical precursors. They also performed better in anti-proliferation by inhibiting the thioredoxin system to induce oxidative stress, and concomitantly to initiate apoptosis in vitro and in vivo. The fabricated arsenicals reversed the hemogram of tumor-bearing mice to normal and eliminated the tumor without causing damage to any organs, exhibiting a good design strategy and pre-clinical application for leukemia and other tumors. MDPI 2022-06-22 /pmc/articles/PMC9266561/ /pubmed/35805931 http://dx.doi.org/10.3390/ijms23136930 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
Shi, Xue-Min
She, Wen-Yan
Liu, Ting-Ting
Gao, Lian-Xun
Liu, Yu-Jiao
Liu, Yi
1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals
title 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals
title_full 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals
title_fullStr 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals
title_full_unstemmed 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals
title_short 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals
title_sort 1,3-benzodioxole derivatives improve the anti-tumor efficiency of arsenicals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266561/
https://www.ncbi.nlm.nih.gov/pubmed/35805931
http://dx.doi.org/10.3390/ijms23136930
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