Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates containing piperazine as inhibitors of PI3K alpha
文献类型：会议论文
| 作者 | Yin, Yong; Zhou, Yang; Sha, Shao; Wu, Xun; Wang, She-Feng; Qiao, Fang; Song, Zhong-Cheng; Zhu, Hai-Liang |
| 出版日期 | 2019 |
| 关键词 | EMBRYONIC LETHALITY PATHWAY KINASE PI3K DISCOVERY 3-KINASES SUBUNIT GROWTH POTENT TARGET |
| 卷号 | 92 |
| DOI | 10.1016/j.bioorg.2019.103238 |
| 英文摘要 | PI3K pathway has been heavily studied and is one of the most potential targets for various cancer treatment. Herein, we designed and synthesized a series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates contained piperazine based on our previous research. They were evaluated for their PI3K alpha wild-type and H1047R mutant inhibitory activities and anticancer effects in vitro. Most of these compounds displayed the potential antiproliferative activities against four cancer cell lines (HCT-116, A549, Huh7 and HL60). Among them, Compound 4p revealed the remarkable antiproliferative activity and was selected for further biological evaluation. Compound 4p displayed the potent activity against both PI3K alpha wild-type and H1047R mutant, and a certain degree of selectivity for PI3K alpha over PI3K beta, gamma and delta, and meanwhile it can remarkable down-regulate the phosphorylation of Akt. In addition, compound 4p was found to induce cell apoptosis via upregulation of Box and cleaved-caspase 3/9, and downregulation of Bcl-2. The above results suggested that compound 4p could be considered as a promising PI3K alpha inhibitor. |
| 学科主题 | Biochemistry & Molecular Biology ; Chemistry |
| ISSN号 | 0045-2068 |
| 源URL | [http://ir.nimte.ac.cn/handle/174433/23319]  |
| 专题 | 会议专题 会议专题_会议论文 |
| 推荐引用方式 GB/T 7714 | Yin, Yong,Zhou, Yang,Sha, Shao,et al. Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates containing piperazine as inhibitors of PI3K alpha[C]. 见:. |
入库方式： OAI收割
来源：宁波材料技术与工程研究所
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