Design, synthesis and biological evaluation of novel oxazole derivatives as potential hypoglycemic agents.

Autor: Wang R; Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan 030001, China; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China., Chen K; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China., Liu S; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China., Ren R; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China., Hou H; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China., Zeng Q; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China., Zhang Y; Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China. Electronic address: yizhang@sxmu.edu.cn., Liu Y; Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan 030001, China. Electronic address: nectarliu@163.com.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Nov 15; Vol. 114, pp. 117961. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1016/j.bmc.2024.117961
Abstrakt: A series of 2,4-disubstituted-oxazole derivatives have been designed and synthesized based on compound 3a, a promising lead compound developed in our lab. Among these derivatives, the optimized compound 5k exhibited potent hypoglycemic activity, increasing glucose consumption by 60 % in HepG2 cells compared to the solvent control, and its activity was higher than that of metformin. Further investigation indicated that compound 5k exhibited negligible cytotoxic effects at a concentration of 25 μM in HepG2 and 3T3-L1 cells and showed moderate inhibitory activity against various subtypes of human cytochrome P450 subtypes. An oral glucose tolerance test confirmed that 5k is an effective hypoglycemic agent. Additionally, mechanistic studies suggested that 5k may exert its hypoglycemic activity through the activation of the AMPK pathway.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ruifeng Wang reports financial support was provided by National Natural Science Foundation of China. Yunfeng Liu reports financial support was provided by National Natural Science Foundation of China. Ruifeng Wang reports financial support was provided by China Postdoctoral Science Foundation. Ruifeng Wnag reports financial support was provided by Shanxi Province Science Foundation for Youths. Yi Zhang reports financial support was provided by Shanxi Provincial Central Leading Local Science and Technology Development Fund Project. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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