2. Academic Validation
  3. Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids

Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids

  • Eur J Med Chem. 2024 Apr 5:269:116311. doi: 10.1016/j.ejmech.2024.116311.
Yu-Qing Meng 1,  Jie Ren 2,  Jing-Xin Sun 2,  Fang-Yan Guo 2,  Jun-Zhe Min 2,  Ji-Xing Nan 3,  Ji-Shan Quan 4,  Li-Hua Lian 5,  Cheng-Hua Jin 6
Affiliations

Affiliations

  • 1 Interdisciplinary Program of Biological Function Molecules, College of Integration Science, Yanbian University, Yanji, 133002, China.
  • 2 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China.
  • 3 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China; Interdisciplinary Program of Biological Function Molecules, College of Integration Science, Yanbian University, Yanji, 133002, China.
  • 4 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China; Interdisciplinary Program of Biological Function Molecules, College of Integration Science, Yanbian University, Yanji, 133002, China. Electronic address: quanjishan@ybu.edu.cn.
  • 5 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China; Interdisciplinary Program of Biological Function Molecules, College of Integration Science, Yanbian University, Yanji, 133002, China. Electronic address: lhlian@ybu.edu.cn.
  • 6 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China; Interdisciplinary Program of Biological Function Molecules, College of Integration Science, Yanbian University, Yanji, 133002, China. Electronic address: jinchenghua@ybu.edu.cn.
PMID: 38508118 DOI: 10.1016/j.ejmech.2024.116311
Abstract

Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various Amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 μM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-β-induced hepatic stellate cells (HSCs), and eventually suppressed HSC activation. Moreover, compound 15g showed a good pharmacokinetic (PK) profile with a favorable half-life (t1/2 = 9.14 h). The results indicated that these compounds exhibited activity targeting ALK5 and may have potential in the treatment of liver fibrosis; thus they are worthy of further study.

Keywords

ALK5; Anti-Liver fibrosis; Imidazole; TGF-β; Thiazole.

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