Department of Chemistry, Faculty of Arts and Sciences, Sakarya University, 54050-Serdivan, Sakarya, Turkey.
Department of Chemistry, Faculty of Arts and Sciences, Sakarya University, 54050-Serdivan, Sakarya, Turkey.
Bioorg Chem. 2020 Aug;101:103969. doi: 10.1016/j.bioorg.2020.103969. Epub 2020 May 24.
The synthesis of seven new ß-amino alcohols was designed and performed by starting from eugenol, a natural phenolic compound known to be biologically active. The synthesized compounds were obtained in yields ranging from 54 to 81%. Molecule structures were determined with FT-IR, H NMR and C NMR spectroscopies. In addition, the inhibitory effects of these substances on acetylcholinesterase (AChE), α-glycosidase (α-Gly), human carbonic anhydrase I (hCA I), and human carbonic anhydrase II (hCA II) enzymes have been investigated. It has been seen that all compounds have a better ability to inhibit compared to existing tried inhibitors. Among these, the best inhibitor against AChE enzyme is 2b (Ki 62.08 ± 11.67 µM and IC 90.33), and against α-Gly, 2c showed the highest effect (Ki 0.33 ± 0.08 µM and IC 0.28). The best inhibitor against hCA I, and hCA II enzymes is compound 2f. For hCA I and hCA II, Ki value was measured as 9.68 ± 1.32 and 11.46 ± 2.64 µM and IC values as 7.37 and 8.26 µM respectively. The interactions of the studied new propanolamine derivatives with the enzymes were done by molecular docking calculations and their biological activities were compared to the experimental tests. Studied enzymes in molecular docking calculations are acetylcholinesterase (AChE) is PDB ID: 4M0E, α-glycosidase (α-Gly) is PDB ID: 1R47, human carbonic anhydrase isoenzyme I (hCA I) PDB ID: 3LXE is human carbonic anhydrase isoenzyme II (hCA II) is PDB ID: 5 AML.
从天然酚类化合物丁香酚出发，设计并进行了 7 种新型β-氨基醇的合成。合成的化合物产率为 54%~81%。通过傅里叶变换红外光谱（FT-IR）、氢核磁共振谱（1H NMR）和碳核磁共振谱（13C NMR）确定了分子结构。此外，还研究了这些物质对乙酰胆碱酯酶（AChE）、α-糖苷酶（α-Gly）、人碳酸酐酶 I（hCA I）和人碳酸酐酶 II（hCA II）的抑制作用。结果表明，与现有抑制剂相比，所有化合物都具有更好的抑制能力。在这些化合物中，对 AChE 酶抑制作用最强的是 2b（Ki 62.08±11.67µM 和 IC90.33），对 α-Gly 抑制作用最强的是 2c（Ki 0.33±0.08µM 和 IC0.28）。对 hCA I 和 hCA II 酶抑制作用最强的抑制剂是化合物 2f。Ki 值分别为 9.68±1.32µM 和 11.46±2.64µM，IC 值分别为 7.37µM 和 8.26µM。通过分子对接计算研究了新的丙醇胺衍生物与酶的相互作用，并将其生物活性与实验测试进行了比较。在分子对接计算中研究的酶是乙酰胆碱酯酶（AChE），PDB ID：4M0E；α-糖苷酶（α-Gly），PDB ID：1R47；人碳酸酐酶同工酶 I（hCA I），PDB ID：3LXE；人碳酸酐酶同工酶 II（hCA II），PDB ID：5 AML。
