Namdaung Umalee, Athipornchai Anan, Khammee Thongchai, Kuno Mayuso, Suksamrarn Sunit
Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand; Center of Excellence for Innovation in Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Chon-Buri 20131, Thailand.
Eur J Med Chem. 2018 Jan 1;143:1301-1311. doi: 10.1016/j.ejmech.2017.10.019. Epub 2017 Oct 12.
In vitro screening for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the Artocarpus lakoocha root-bark extracts revealed interesting results. Bioassay-guided fractionation resulted in the isolation of two new (1 and 2) and six known 2-arylbenzofurans 3-8, along with one stilbenoid 9 and one flavonoid 10. The structures of the isolated compounds were elucidated by UV, IR, 1D- and 2D-NMR and MS spectroscopic data analysis. Compounds 4, 6 and 7 exhibited more potent AChE inhibitory activity (IC = 0.87-1.10 μM) than the reference drug, galantamine. Compounds 4, 8 and 9 displayed greater BChE inhibition than the standard drug. The preferential inhibition of BChE over AChE indicated that 4 also showed a promising dual AChE and BChE inhibitor. The synthetic mono-methylated analogs 4a-c and 6a-b were found to be good BChE inhibitors with IC values ranging between 0.31 and 1.11 μM. Based on the docking studies, compounds 4 and 6 are well-fitted in the catalytic triad of AChE. Compounds 4 and 6 showed different binding orientations on BChE, and the most potent BChE inhibitor 4 occupied dual binding to both CAS and PAS more efficiently.
对波罗蜜树根皮提取物的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）抑制活性进行体外筛选，结果令人感兴趣。生物测定导向的分级分离得到了两种新的化合物（1和2）、六种已知的2-芳基苯并呋喃（3-8）、一种二苯乙烯类化合物（9）和一种黄酮类化合物（10）。通过紫外光谱、红外光谱、一维和二维核磁共振光谱以及质谱数据分析确定了分离得到的化合物的结构。化合物4、6和7表现出比参比药物加兰他敏更强的AChE抑制活性（IC = 0.87 - 1.10 μM）。化合物4、8和9表现出比标准药物更强的BChE抑制活性。对BChE的优先抑制超过AChE表明4也是一种有前景的双重AChE和BChE抑制剂。发现合成的单甲基化类似物4a - c和6a - b是良好的BChE抑制剂，IC值在0.31至1.11 μM之间。基于对接研究，化合物4和6很好地契合在AChE的催化三联体中。化合物4和6在BChE上表现出不同的结合取向，最有效的BChE抑制剂4更有效地占据了与CAS和PAS的双重结合。
