6-氮杂吲哚类化合物的合成及抗胰腺癌活性评价
Synthesis and activity evaluation of 6-azazindole derivatives for pancreatic cancer therapy
曹阳 1李前 2王亚玲 2崔文慧 2钱晨亮 2司鑫鑫2
作者信息
- 1. 南京大学化学化工学院,江苏南京 210093;江苏海洋大学,江苏省海洋药物活性分子筛选重点实验室,江苏连云港 222005
- 2. 江苏海洋大学,江苏省海洋药物活性分子筛选重点实验室,江苏连云港 222005
- 折叠
摘要
通过筛选内部化合物库,鉴定出了具有一定抗胰腺癌活性的片段.经系统改造合成了 4类共计18个化合物,并进行了抗胰腺癌活性评价.化合物 Ⅱ-1(IC50=6.40±0.34 μmol·L-1)和 Ⅱ-2(IC50=7.15±0.51 μmol·L-1)活性表现突出.随后用细胞划痕实验及侵袭实验评价了 Ⅱ-1的抗迁移能力及侵袭能力,结果显示,Ⅱ-1具有良好的抗迁移能力及突出的抗侵袭能力.利用分子对接技术及分子动力学模拟技术,锁定了 Ⅱ-1的靶点为双特异性酪氨酸磷酸化调控激酶1A(DYRK1A).经酶活测试Ⅱ-1和Ⅱ-2分别有48％及32％酶抑制能力.
Abstract
Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library.Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated.Ⅱ-1(IC50=6.40±0.34 μmol·L-1)and Ⅱ-2(IC50=7.15±0.51 μmol·L-1)exhibited outstanding activity.Subsequently,the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay,Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability.Using molecular docking technology and molecular dynamics simulation technology,the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A(DYRK1A).By enzyme activity testing,the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48％and 32％,respectively.
关键词
6-氮杂吲哚/抗胰腺癌/双特异性酪氨酸磷酸化调控激酶1A/合成/抗增殖Key words
6-azaindole/anti-pancreatic cancer/bispecific tyrosine phosphorylation regulates kinase 1A/synthesis/anti-proliferation引用本文复制引用
基金项目
江苏海洋大学研究生科研与实践创新计划项目(KYCX2022-31)
中国博士后科学基金(2023M741444)
出版年
2024
NETL
NSTL
万方数据