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

Yu-Qing Meng¹, Jie Ren², Jing-Xin Sun², Fang-Yan Guo², Jun-Zhe Min², Ji-Xing Nan³, Ji-Shan Quan⁴, Li-Hua Lian⁵, Cheng-Hua Jin⁶

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

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

Yu-Qing Meng et al. Eur J Med Chem. 2024.

. 2024 Apr 5:269:116311.

doi: 10.1016/j.ejmech.2024.116311. Epub 2024 Mar 13.

Authors

Yu-Qing Meng¹, Jie Ren², Jing-Xin Sun², Fang-Yan Guo², Jun-Zhe Min², Ji-Xing Nan³, Ji-Shan Quan⁴, Li-Hua Lian⁵, Cheng-Hua Jin⁶

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 (t_1/2 = 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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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources