- Design and Synthesis of Novel N-(2-aminophenyl)benzamide Derivatives as Histone Deacetylase Inhibitors and Their Antitumor Activity Study
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Histone deacetylases (HDACs) are promising therapeutic targets for cancer therapy because inhibition of HDACs triggers growth arrest or apoptosis of tumor cells. In the present study, a new series of fluorinated N-(2-aminophenyl)benzamide derivatives were synthesized to investigate potential inhibition of HDACs and associated anticancer activity. Among the synthesized derivatives, compound 24a showed potent inhibitory activity of HDACs and higher antitumor efficacy in human cancer cell lines (HCT-116, MCF-7, and A549) compared with SAHA. Moreover, animal studies demonstrated that compound 24a showed potent in vivo antitumor efficacy in an HCT-116 colon cancer xenograft mouse model.
- La, Minh Thanh,Jeong, Byung-Hoon,Kim, Hee-Kwon
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p. 740 - 743
(2021/03/16)
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- Selective HDAC inhibitors with potent oral activity against leukemia and colorectal cancer: Design, structure-activity relationship and anti-tumor activity study
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Previously, we reported the discovery of a series of N-hydroxycinnamamide-based HDAC inhibitors, among which compound 11y exhibited high HDAC1/3 selectivity. In this current study, structural derivatization of 11y led to a new series of benzamide based HDAC inhibitors. Most of the compounds exhibited high HDACs inhibitory potency. Compound 11a (with 4-methoxybenzoyl as N-substituent in the cap and 4-(aminomethyl) benzoyl as the linker group) exhibited selectivity against HDAC1 to some extent, and showed potent antiproliferative activity against several tumor cell lines. In?vivo studies revealed that compound 11a displayed potent oral antitumor activity in both hematological tumor cell U937 xenograft model and solid tumor cell HCT116 xenograft model with no obvious toxicity. Further modification of benzamide 3, 11a and 19 afforded new thienyl and phenyl compounds (50a, 50b, 63a, 63b and 63c) with dramatic HDAC1 and HDAC2 dual selectivity, and the fluorine containing compound 56, with moderate HDAC3 selectivity.
- Li, Xiaoyang,Zhang, Yingjie,Jiang, Yuqi,Wu, Jingde,Inks, Elizabeth S.,Chou, C. James,Gao, Shuai,Hou, Jinning,Ding, Qinge,Li, Jingyao,Wang, Xue,Huang, Yongxue,Xu, Wenfang
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p. 185 - 206
(2017/04/21)
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- Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups
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As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605?μM, respectively), compound 9n with IC50 values of 0.032, 0.256 and 0.311?μM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity.
- Gao, Shuai,Zang, Jie,Gao, Qianwen,Liang, Xuewu,Ding, Qinge,Li, Xiaoyang,Xu, Wenfang,Chou, C. James,Zhang, Yingjie
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p. 2981 - 2994
(2017/05/25)
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- Image-guided synthesis reveals potent blood-brain barrier permeable histone deacetylase inhibitors
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Recent studies have revealed that several histone deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance
- Seo, Young Jun,Kang, Yeona,Muench, Lisa,Reid, Alicia,Caesar, Shannon,Jean, Logan,Wagner, Florence,Holson, Edward,Haggarty, Stephen J.,Weiss, Philipp,King, Payton,Carter, Pauline,Volkow, Nora D.,Fowler, Joanna S.,Hooker, Jacob M.,Kim, Sung Won
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p. 588 - 596
(2014/08/05)
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- SILICON DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
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The present invention relates to a novel class of Silicon derivatives. The Silicon compounds can be used to treat cancer. The Silicon compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation,
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Page/Page column 56
(2009/04/25)
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- 4-CARBOXYBENZYLAMINO DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
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The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selecti
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- PHOSPHORUS DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
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The present invention relates to a novel class of phosphorus derivatives. The phosphorus compounds can be used to treat cancer. The phosphorus compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differe
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Page/Page column 167
(2008/06/13)
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- Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2)
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A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC i
- Witter, David J.,Harrington, Paul,Wilson, Kevin J.,Chenard, Melissa,Fleming, Judith C.,Haines, Brian,Kral, Astrid M.,Secrist, J. Paul,Miller, Thomas A.
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p. 726 - 731
(2008/12/23)
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