دورية أكاديمية
Discovery of novel polysubstituted N-alkyl acridone analogues as histone deacetylase isoform-selective inhibitors for cancer therapy
العنوان: | Discovery of novel polysubstituted N-alkyl acridone analogues as histone deacetylase isoform-selective inhibitors for cancer therapy |
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المؤلفون: | Ze Wang, Li Zhao, Bo Zhang, Jiahe Feng, Yule Wang, Bin Zhang, Haixiao Jin, Lijian Ding, Ning Wang, Shan He |
المصدر: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 38, Iss 1 (2023) |
بيانات النشر: | Taylor & Francis Group, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Therapeutics. Pharmacology |
مصطلحات موضوعية: | Design and synthesis, hit compound, anticancer, histone deacetylases, isoform-selective inhibitors, Therapeutics. Pharmacology, RM1-950 |
الوصف: | AbstractPan-histone deacetylase (HDAC) inhibitors often have some toxic side effects. In this study, three series of novel polysubstituted N-alkyl acridone analogous were designed and synthesised as HDAC isoform-selective inhibitors. Among them, 11b and 11c exhibited selective inhibition of HDAC1, HDAC3, and HDAC10, with IC50 values ranging from 87 nM to 418 nM. However, these compounds showed no inhibitory effect against HDAC6 and HDAC8. Moreover, 11b and 11c displayed potent antiproliferative activity against leukaemia HL-60 cells and colon cancer HCT-116 cells, with IC50 values ranging from 0.56 μM to 4.21 μM. Molecular docking and energy scoring functions further analysed the differences in the binding modes of 11c with HDAC1/6. In vitro anticancer studies revealed that the hit compounds 11b and 11c effectively induced histone H3 acetylation, S-phase cell cycle arrest, and apoptosis in HL-60 cells in a concentration-dependent manner. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 14756366 1475-6374 1475-6366 |
Relation: | https://doaj.org/toc/1475-6366; https://doaj.org/toc/1475-6374 |
DOI: | 10.1080/14756366.2023.2206581 |
URL الوصول: | https://doaj.org/article/777434e115ee4310935bd674c4639a0a |
رقم الأكسشن: | edsdoj.777434e115ee4310935bd674c4639a0a |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14756366 14756374 |
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DOI: | 10.1080/14756366.2023.2206581 |