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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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/6930 |
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| author | Xue-Min Shi Wen-Yan She Ting-Ting Liu Lian-Xun Gao Yu-Jiao Liu Yi Liu |
| author_facet | Xue-Min Shi Wen-Yan She Ting-Ting Liu Lian-Xun Gao Yu-Jiao Liu Yi Liu |
| author_sort | Xue-Min Shi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T21:51:33Z |
| format | Article |
| id | doaj.art-222b35a16d8f45ad8607d6b68ff3bb75 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:51:33Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-222b35a16d8f45ad8607d6b68ff3bb752023-11-23T20:04:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313693010.3390/ijms231369301,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of ArsenicalsXue-Min Shi0Wen-Yan She1Ting-Ting Liu2Lian-Xun Gao3Yu-Jiao Liu4Yi Liu5College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, ChinaCollege of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Separation Membranes and Membrane Processes, School of Chemistry, Tiangong University, Tianjin 300387, ChinaCollege of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Separation Membranes and Membrane Processes, School of Chemistry, Tiangong University, Tianjin 300387, ChinaCollege of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, ChinaArsenicals 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.https://www.mdpi.com/1422-0067/23/13/6930organic arsenicalsTrxRROSdocking4T1 tumorstiripentol |
| spellingShingle | Xue-Min Shi Wen-Yan She Ting-Ting Liu Lian-Xun Gao Yu-Jiao Liu Yi Liu 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals International Journal of Molecular Sciences organic arsenicals TrxR ROS docking 4T1 tumor stiripentol |
| 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 | organic arsenicals TrxR ROS docking 4T1 tumor stiripentol |
| url | https://www.mdpi.com/1422-0067/23/13/6930 |
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