Synthesis and activity evaluation of 6-azazindole derivatives for pancreatic cancer therapy
10.16438/j.0513-4870.2024-0135
- VernacularTitle:6-氮杂吲哚类化合物的合成及抗胰腺癌活性评价
- Author:
Yang CAO
1
;
Qian LI
2
;
Ya-ling WANG
2
;
Wen-hui CUI
2
;
Chen-liang QIAN
2
;
Xin-xin SI
2
Author Information
1. School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang 222005, China
2. Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang 222005, China
- Publication Type:Research Article
- Keywords:
6-azaindole;
anti-pancreatic cancer;
bispecific tyrosine phosphorylation regulates kinase 1A;
synthesis;
anti-proliferation
- From:
Acta Pharmaceutica Sinica
2024;59(10):2828-2835
- CountryChina
- Language:Chinese
-
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.
