دورية أكاديمية
Discovery of Quinacrine as a Potent Topo II and Hsp90 Dual-Target Inhibitor, Repurposing for Cancer Therapy
| العنوان: | Discovery of Quinacrine as a Potent Topo II and Hsp90 Dual-Target Inhibitor, Repurposing for Cancer Therapy |
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| المؤلفون: | Xin Pan, Teng-yu Mao, Yan-wen Mai, Cheng-cheng Liang, Wei-hao Huang, Yong Rao, Zhi-shu Huang, Shi-liang Huang |
| المصدر: | Molecules, Vol 27, Iss 17, p 5561 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Organic chemistry |
| مصطلحات موضوعية: | HSP90 inhibitor, dual−target inhibitor, topo II inhibitor, quinacrine, the N−ATPase domains, Organic chemistry, QD241-441 |
| الوصف: | Topo II and Hsp90 are promising targets. In this study, we first verified the structural similarities between Topo IIα ATPase and Hsp90α N−ATPase. Subsequently, 720 compounds from the Food and Drug Administration (FDA) drug library and kinase library were screened using the malachite green phosphate combination with the Topo II-mediated DNA relaxation and MTT assays. Subsequently, the antimalarial drug quinacrine was found to be a potential dual−target inhibitor of Topo II and Hsp90. Mechanistic studies showed that quinacrine could specifically bind to the Topo IIα ATPase domain and inhibit the activity of Topo IIα ATPase without impacting DNA cleavage. Furthermore, our study revealed that quinacrine could bind Hsp90 N−ATPase and inhibit Hsp90 activity. Significantly, quinacrine has broad antiproliferation activity and remains sensitive to the multidrug−resistant cell line MCF−7/ADR and the atypical drug−resistant tumor cell line HL−60/MX2. Our study identified quinacrine as a potential dual−target inhibitor of Topo II and Hsp90, depending on the ATP−binding domain, positioning it as a hit compound for further structural modification. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 27175561 1420-3049 |
| Relation: | https://www.mdpi.com/1420-3049/27/17/5561; https://doaj.org/toc/1420-3049 |
| DOI: | 10.3390/molecules27175561 |
| URL الوصول: | https://doaj.org/article/d57ae07bd94249d987c71b314455d0d3 |
| رقم الأكسشن: | edsdoj.57ae07bd94249d987c71b314455d0d3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 27175561 14203049 |
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| DOI: | 10.3390/molecules27175561 |