Department of Organic Chemistry, Institute of Chemical Sciences, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovakia.
Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Košice, Slovakia.
Bioorg Chem. 2023 Aug;137:106636. doi: 10.1016/j.bioorg.2023.106636. Epub 2023 May 27.
Herein we report the synthesis of new furanoid sugar amino acids and thioureas, prepared by coupling aromatic amino acids and dipeptides with isothiocyanato- functionalized ribofuranose ring. Since carbohydrate-derived structures possess many biological activities, synthesized compounds were evaluated as anti-amyloid and antioxidant agents. The anti-amyloid activity of the studied compounds was evaluated based on their potential to destroy amyloid fibrils of intrinsically disordered Aβ peptide and globular hen egg-white (HEW) lysozyme. The destructive efficiency of the compounds differed between the studied peptides. While the destruction activity of the compounds on the HEW lysozyme amyloid fibrils was negligible, the effect on Aβ amyloid fibrils was significantly higher. Furanoid sugar α-amino acid 1 and its dipeptide derivatives 8 (Trp-Trp) and 11 (Trp-Tyr) were the most potent anti-Aβ fibrils compounds. The antioxidant properties of synthesized compounds were estimated by three complementary in vitro assays (DPPH, ABTS, and FRAP). The ABTS assay was the most sensitive for assessing the radical scavenging activity of all tested compounds compared to the DPPH test. Significant antioxidant activity was detected for compounds in the group of aromatic amino acids depending on the present amino acid, with the highest activity in the case of dipeptides 11 and 12 containing the Tyr and Trp moiety. Regarding the FRAP assay, the best reducing antioxidant potential revealed Trp-containing compounds 5, 10, and 12.
在此，我们报告了新的呋喃糖氨基酸和硫脲的合成，它们是通过将芳香族氨基酸和二肽与异硫氰酸酯官能化的呋喃核糖环偶联制备的。由于碳水化合物衍生的结构具有许多生物活性，因此合成的化合物被评估为抗淀粉样蛋白和抗氧化剂。研究化合物的抗淀粉样蛋白活性是基于它们破坏无规卷曲 Aβ肽和球状鸡卵清溶菌酶固有无序淀粉样纤维的潜力来评估的。研究的化合物对不同肽的破坏效率不同。虽然化合物对 HEW 溶菌酶淀粉样纤维的破坏活性可以忽略不计，但对 Aβ 淀粉样纤维的影响明显更高。呋喃糖 α-氨基酸 1 及其二肽衍生物 8（色氨酸-色氨酸）和 11（色氨酸-酪氨酸）是最有效的抗 Aβ 纤维化合物。通过三种互补的体外测定法（DPPH、ABTS 和 FRAP）评估了合成化合物的抗氧化性能。与 DPPH 试验相比，ABTS 试验对所有测试化合物的自由基清除活性最敏感。在包含芳香族氨基酸的组中，根据存在的氨基酸检测到显著的抗氧化活性，含有 Tyr 和 Trp 部分的二肽 11 和 12 的活性最高。关于 FRAP 测定，含 Trp 的化合物 5、10 和 12 显示出最佳的还原抗氧化潜力。
