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XU Yuantao, WANG Jundong, GUAN Li, ZHAO Ning, LI Weize. Synthesis and antidiabetic activity evaluation of benzopyrimidine derivatives[J]. Journal of China Pharmaceutical University, 2023, 54(5): 569-576. DOI: 10.11665/j.issn.1000-5048.2023041701
Citation: XU Yuantao, WANG Jundong, GUAN Li, ZHAO Ning, LI Weize. Synthesis and antidiabetic activity evaluation of benzopyrimidine derivatives[J]. Journal of China Pharmaceutical University, 2023, 54(5): 569-576. DOI: 10.11665/j.issn.1000-5048.2023041701
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Synthesis and antidiabetic activity evaluation of benzopyrimidine derivatives

  • 1.

    Shaanxi Panlong Pharmaceutical Group Co., Ltd., Zhashui 714000

  • 2.

    Shandong Yantai Food and Drug Inspection and Testing Center, Yantai 264000

  • 3.

    College of Pharmacy, Xi'an Medical University, Xi'an 710021, China

Funds: This study was supported by the National Natural Science Foundation of China (No.82004075); the Project of Shaanxi Provincial Department of Science and Technology (No.2023-JC-QN-0827); the Youth Innovation Team Construction Project for Universities in Shaanxi Province (Shaanxi Education [2019] No.90); and the Science and Technology Innovation Team Project of Xi’an Medical University (No.2021TDPT04)
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  • Received Date: April 16, 2023
  • Revised Date: October 17, 2023
    Graphical Abstract
    • Abstract
  • Thioredoxin-interacting protein (TXNIP), which mainly regulates glucose homeostasis in pancreatic β cells, is a novel target in the treatment of diabetes.In this study, 4-hydroxybenzopyrimidine was used as the raw material, four nitrogen-containing rings (imidazole, methylpiperazine, pyrazole, morpholine) were introduced, benzopyrimidine skeleton with nitrogen-containing rings derivatives targeting TXNIP was designed and synthesized, and the protective effect of compounds on palmitic acid-stimulated islet β cells was investigated.A total of 20 benzopyrimidine derivatives were designed and synthesized, and the structures were confirmed by 1H NMR and ESI-MS.Pharmacological studies showed that most of the compounds exhibited protective effects on islet β cells, with better axtivity for compounds C-1, C-2, C-4 and D-2 (cell survival rate > 70%) compared with PA model group (38.3%), Among the four compounds, D-2 had the highest activity of 87.2%, so it could become a potential new anti-diabetic chemical entity.
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    • References (11)
  • [1]
    Guthrie RA, Guthrie DW. Pathophysiology of diabetes mellitus[J]. Crit Care Nurs Q, 2004, 27(2): 113-125.
    [2]
    Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues[J]. Free Radic Biol Med, 1996, 20(3): 463-466.
    [3]
    Kehm R, J?hnert M, Deubel S, et al. Redox homeostasis and cell cycle activation mediate beta-cell mass expansion in aged, diabetes-prone mice under metabolic stress conditions: role of thioredoxin-interacting protein (TXNIP)[J]. Redox Biol, 2020, 37: 101748.
    [4]
    Chen JQ, Couto FM, Minn AH, et al. Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-interacting protein[J]. Biochem Biophys Res Commun, 2006, 346(3): 1067-1074.
    [5]
    Nishiyama A, Matsui M, Iwata S, et al. Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression[J]. J Biol Chem, 1999, 274(31): 21645-21650.
    [6]
    Junn E, Han SH, Im JY, et al. Vitamin D3 up-regulated protein 1 mediates oxidative stress via suppressing the thioredoxin function[J]. J Immunol, 2000, 164(12): 6287-6295.
    [7]
    Schulze PC, Yoshioka J, Takahashi T, et al. Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein[J]. J Biol Chem, 2004, 279(29): 30369-30374.
    [8]
    Shalev A, Pise-Masison CA, Radonovich M, et al. Oligonucleotide microarray analysis of intact human pancreatic islets: identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway[J]. Endocrinology, 2002, 143(9): 3695-3698.
    [9]
    Shalev A. Lack of TXNIP protects beta-cells against glucotoxicity[J]. Biochem Soc Trans, 2008, 36(Pt 5): 963-965.
    [10]
    Thielen LA, Chen JQ, Jing G, et al. Identification of an anti-diabetic, orally available small molecule that regulates TXNIP expression and glucagon action[J]. Cell Metab, 2020, 32(3): 353-365.
    [11]
    Zheng S, Chen NX, Kang XJ, et al. Irisin alleviates FFA induced β-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway[J]. Endocrine, 2022, 75(3):740-751.
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