A novel aromatic amide derivative SY-65 co-targeted tubulin and histone deacetylase 1 with potent anticancer activity in vitro and in vivo
文献类型：期刊论文
| 作者 | Li, Yin-Ru1; Liu, Fang-Fang3; Liu, Wen-Bo2; Zhang, Yi-Fan2; Tian, Xin-Yi1; Fu, Xiang-Jing1; Xu, Yan1; Song, Jian1,2; Zhang, Sai-Yang1,2,4 |
| 刊名 | BIOCHEMICAL PHARMACOLOGY
 |
| 出版日期 | 2022-07 |
| 卷号 | 201页码:115070 |
| ISSN号 | 0006-2952 |
| 关键词 | Epigenetic regulation Tubulin HDAC Anticancer activity |
| DOI | 10.1016/j.bcp.2022.115070 |
| 文献子类 | Article |
| 英文摘要 | Given the essential role of Epigenetic regulation in many biological processes, targeted epigenetic drugs have been gradually applied to the treatment of tumors. Histone deacetylases (HDACs) are a class of epigenetic enzymes, which play key roles in chromosome structural modification and gene expression regulation. Targeted microtubules drugs have achieved great success in clinical application for decades. Development of novel agents with multitargeting capabilities specially dual-target has become a popular research field for the treatment of human cancers, which may provide synergistic anticancer effects. Here, we reported a novel aromatic amide derivative SY-65 co-targeted tubulin and histone deacetylase 1 with potent anticancer activity in vitro and in vivo. Compound SY-65 was identified as a dual inhibitor of tubulin/HDAC1 (IC50 = 3.64 and 0.529 mu M, respectively) with excellent antiproliferative activity against MGC-803, HCT-116, KYSE-450, HGC-27, SGC-7901 and MKN-45 cells. Especially, compound SY-65 exhibited potent antiproliferative activity against MGC-803, HGC-27 and SGC7901 cells with IC50 values < 55 nM, which was better than that of Colchicine, MS-275 and SAHA. Compound SY-65 effectively inhibited tubulin polymerization and bound to the colchicine binding site of tubulin, as well as inhibited HDAC1 activity both intra/extracellularly. Molecular docking results suggested there were the welldefined binding modes of compound SY-65 in HDAC1 and tubulin. In addition, compound SY-65 inhibited colony formation, interfered with the cell cycle distribution, induced cell cycle arrest at the G2/M phase and apoptosis in MGC-803 and HGC-27 cells. Compound SY-65 also exhibited a good tumor inhibitory effect in vivo without obvious toxicity. Therefore, compound SY-65 could be developed as a novel tubulin/HDAC1 candidate inhibitor for future cancer therapeutics. |
| WOS关键词 | INHIBITORS ; CANCER ; EPIGENETICS ; MECHANISMS ; DISCOVERY ; AGENTS ; HDAC |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:000800017100004 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309349]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Song, Jian; Zhang, Sai-Yang |
| 作者单位 | 1.Zhengzhou Univ, Sch Basic Med Sci, Zhengzhou 450001, Peoples R China; 2.Zhengzhou Univ, Inst Drug Discovery & Dev, Sch Pharmaceut Sci, Key Lab Adv Drug Preparat Technol,Minist Educ, Zhengzhou 450001, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yin-Ru,Liu, Fang-Fang,Liu, Wen-Bo,et al. A novel aromatic amide derivative SY-65 co-targeted tubulin and histone deacetylase 1 with potent anticancer activity in vitro and in vivo[J]. BIOCHEMICAL PHARMACOLOGY,2022,201:115070. |
| APA | Li, Yin-Ru.,Liu, Fang-Fang.,Liu, Wen-Bo.,Zhang, Yi-Fan.,Tian, Xin-Yi.,...&Zhang, Sai-Yang.(2022).A novel aromatic amide derivative SY-65 co-targeted tubulin and histone deacetylase 1 with potent anticancer activity in vitro and in vivo.BIOCHEMICAL PHARMACOLOGY,201,115070. |
| MLA | Li, Yin-Ru,et al."A novel aromatic amide derivative SY-65 co-targeted tubulin and histone deacetylase 1 with potent anticancer activity in vitro and in vivo".BIOCHEMICAL PHARMACOLOGY 201(2022):115070. |
入库方式： OAI收割
来源：上海药物研究所
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