International Institute of Rare Sugar Research and Education, Kagawa University, Miki, Kagawa 761-0795, Japan.
Kagawa Prefectural Research Institute for Environmental Sciences and Public Health, Takamatsu, Kagawa 760-0065, Japan.
Bioorg Med Chem Lett. 2019 Sep 1;29(17):2483-2486. doi: 10.1016/j.bmcl.2019.07.017. Epub 2019 Jul 16.
The biological activities of deoxy sugars (deoxy monosaccharides) have remained largely unstudied until recently. We compared the growth inhibition by all 1-deoxyketohexoses using the animal model Caenorhabditis elegans. Among the eight stereoisomers, 1-deoxy-d-allulose (1d-d-Alu) showed particularly strong growth inhibition. The 50% inhibition of growth (GI) concentration by 1d-d-Alu was estimated to be 5.4 mM, which is approximately 10 times lower than that of d-allulose (52.7 mM), and even lower than that of the potent glycolytic inhibitor, 2-deoxy-d-glucose (19.5 mM), implying that 1d-d-Alu has a strong growth inhibition. In contrast, 5-deoxy- and 6-deoxy-d-allulose showed no growth inhibition of C. elegans. The inhibition by 1d-d-Alu was alleviated by the addition of d-ribose or d-fructose. Our findings suggest that 1d-d-Alu-mediated growth inhibition could be induced by the imbalance in d-ribose metabolism. To our knowledge, this is the first report of biological activity of 1d-d-Alu which may be considered as an antimetabolite drug candidate.
直到最近，脱氧糖（脱氧单糖）的生物活性在很大程度上仍未得到研究。我们使用秀丽隐杆线虫动物模型比较了所有 1-脱氧酮己糖的生长抑制作用。在这 8 个立体异构体中，1-脱氧-d-阿洛酮糖（1d-d-Alu）表现出特别强的生长抑制作用。1d-d-Alu 的 50%生长抑制浓度（GI）估计为 5.4mM，约比 d-阿洛酮糖（52.7mM）低 10 倍，甚至比强糖酵解抑制剂 2-脱氧-d-葡萄糖（19.5mM）低，这意味着 1d-d-Alu 具有很强的生长抑制作用。相比之下，5-脱氧和 6-脱氧-d-阿洛酮糖对线虫的生长没有抑制作用。1d-d-Alu 的抑制作用可以通过添加 d-核糖或 d-果糖来缓解。我们的发现表明，1d-d-Alu 介导的生长抑制可能是由 d-核糖代谢失衡引起的。据我们所知，这是 1d-d-Alu 生物活性的首次报道，它可能被视为一种抗代谢药物候选物。
