Synthesis and antidiabetic activity evaluation of benzopyrimidine-7-azaindole derivatives targeting TXNIP/DYRK1A
10.11665/j.issn.1000-5048.2025061601
- VernacularTitle:靶向TXNIP/DYRK1A的苯并嘧啶-7-氮杂吲哚衍生物的合成及抗糖尿病活性评价
- Author:
Yucan CUI
1
;
Yaning WANG
;
Jing WANG
;
Aiyun LI
;
Wanzhen SU
;
Hong HE
;
Weize LI
;
Li GUAN
Author Information
1. 西安医学院药学院, 西安710021;山西医科大学生理学系, 细胞生理学教育部重点实验室, 太原 030001
- Publication Type:Journal Article
- Keywords:
diabetes;
thioredoxin-interacting protein;
dual-specificity tyrosine phosphatase regulator kinase 1A;
benzopyrimidine-7-azaindole derivatives;
islet β cells
- From:
Journal of China Pharmaceutical University
2026;57(4):453-459
- CountryChina
- Language:Chinese
-
Abstract:
Thioredoxin-interacting protein(TXNIP) inhibitors can inhibit the apoptosis of pancreatic β cells, while dual-specificity tyrosine-phosphoryation-regulated kinase 1A (DYRK1A) inhibitors can promote the proliferation of pancreatic β cells. This study used 4-benzopyrimidine as the starting material to design and synthesize benzopyrimidine-7-azaindole scaffold derivatives targeting TXNIP/DYRK1A by linking it with variously substituted 7-azaindoles via carbon chains of different lengths. A total of 12 novel quinazoline-7-azaindole derivatives were designed and synthesized, their structures confirmed by 1H NMR and ESI-MS, and their content was determined by HPLC. Pharmacological activity assays demonstrated that all 12 compounds exhibited inhibitory effects on β-cell apoptosis, with YN-3 and YN-6 showing the strongest activity, achieving a cell survival rate exceeding 75% (compared to 43.08% in the control group). Proliferation-promoting experiments revealed that most compounds exhibited proliferative activity, with YN-1–YN-3 and YN-11 demonstrating proliferation enhancement rates greater than 125%. YN-3exhibited the strongest combined anti-apoptotic and proliferation-promoting activities and may represent a promising new chemical entity for antidiabetic drug development.
