Synthesis and evaluation of 5-aminimidazole-4-carboxamide riboside derivatives as anti-fatigue agents

Autor: Huimin Zhu, Wanbo Zeng, Tangna Zhao, Weiguo Shi, Xiao Dong, Aiping Zhang, Xiang Li, Liang Xu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Arabian Journal of Chemistry, Vol 15, Iss 12, Pp 104313- (2022)
Druh dokumentu: article
ISSN: 1878-5352
DOI: 10.1016/j.arabjc.2022.104313
Popis: Fatigue has a negative influence on daily life and work, and serious or chronic fatigue can even cause health problems. Studies have shown that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) can exert anti-fatigue effects by activating AMP-activated protein kinase (AMPK). In this study, six AICAR derivatives with substitution at the hydroxyl sites of the ribose moiety were synthesized and evaluated as anti-fatigue agents. All of the derivatives were demonstrated to effectively resist fatigue in animal models. The mice treated with the optimal compound ZHM-01 showed an 8.6-fold greater exhaustion distance in the running wheel test and a 5.1-fold greater exhaustion time in the weight-loaded swimming test than those of the blank control group. ZHM-01 treatment also reduced lactic acid (LA) and blood urea nitrogen (BUN) accumulation during exercise. In addition, ZHM-01 administration enhanced the phosphorylation of AMPK but did not excite the central nervous system. Moreover, ZHM-01 showed good biological safety in a 21-day toxicity evaluation. This study provides a new reference for the development of treatments for fatigue-related health problems.
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