氮杂吖啶衍生物作为EGFR和Src抑制剂的设计合成与抗癌活性研究
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- 英文论文题名：Design,Synthesis and Evaluate N-hetero-acridine derivatives as EGFR and Src kinase inhibitors for anti-tumor treatment
- 论文作者：崔志闪 ; 高春梅 ; 蒋宇扬
- 英文论文作者：Zhishan Cui ; Chunmei Gao ; Yuyang Jiang ; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology ; The Graduate School at Shenzhen ; Tsinghua University
- 年：2016
- 作者机构：清华大学深圳研究生院,深圳市化学生物学重点实验室-省部共建国家重点实验室培育基地;
- 论文关键词：EGFR ; Src ; 氮杂吖啶类衍生物
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：TQ460.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：213k
- 原文格式：D
- 会议级别：全国
摘要
蛋白激酶在肿瘤细胞中的异常表达与肿瘤新生血管的生成、肿瘤的侵袭和转移、肿瘤的化疗抗性等密切相关。因此,以蛋白激酶为靶点进行抗肿瘤药物设计是目前研究的热点,已有多个药物上市。表皮生长因子受体EGFR和肉瘤病毒基因Src属于蛋白质酪氨酸激酶家族。临床研究表明EGFR和Src在肿瘤生长信号中起协同作用,联合应用两者抑制剂可对多种肿瘤如三阴性乳腺癌,胰腺癌等取得更有效的治疗效果~1,但是目前对于EGFR和Src双靶点抑制剂研究没有相关报道。结合EGFR和Src抑制剂的研究现状及计算机辅助药物的设计方法,我们将吖啶化合物的结构~2进行进一步改造,设计氮杂吖啶类化合物为潜在的EGFR和Src双靶点小分子抑制剂,该类化合物可较好抑制肿瘤细胞如K562细胞的活性,后续生物学活性评价实验还在研究中。
Overexpression of protein kinases are intimately involved in tumour cell angiogenesis,invasion,metastasis and chemoresistance.Therefore,compounds targeted protein kinases have become a hot spot,and now many drugs have been approved to market.EGFR and Src belong to the Protein Tyrosine Kinase family.As Src and EGFR display synergistic effect in tumor clinical research,such as triple negative breast cancer,pancreatic cancer,it is important to design inhibitors targeted both Src and EGFR.As a follow-up of our previous studies,based on literature and using molecular docking method,we designed and synthesized a new series of N- hetero- acridine derivatives as potential novel dual EGFR and Src inhibitors,some of which displayed good antiproliferative activity against K562 cells.Further experiments about the bioactivity are going on.
Overexpression of protein kinases are intimately involved in tumour cell angiogenesis,invasion,metastasis and chemoresistance.Therefore,compounds targeted protein kinases have become a hot spot,and now many drugs have been approved to market.EGFR and Src belong to the Protein Tyrosine Kinase family.As Src and EGFR display synergistic effect in tumor clinical research,such as triple negative breast cancer,pancreatic cancer,it is important to design inhibitors targeted both Src and EGFR.As a follow-up of our previous studies,based on literature and using molecular docking method,we designed and synthesized a new series of N- hetero- acridine derivatives as potential novel dual EGFR and Src inhibitors,some of which displayed good antiproliferative activity against K562 cells.Further experiments about the bioactivity are going on.
引文
[1]Luigi Formisano,Lucia Nappi,Roberta Rosa,Roberta Marciano,Breast Cancer Res.2014,16:R45
[2]Zhishan Cui,Xi Li,Lulu Li,Bin Zhang,Bioorg.Med.Chem.2016.24:261.
[2]Zhishan Cui,Xi Li,Lulu Li,Bin Zhang,Bioorg.Med.Chem.2016.24:261.