Abstract：
Six known products (4-9) were prepared from reaction of adipoyl chloride with 1,2,3-trimethoxybenzene according to the literature. From (2,3,4-trimethoxyphenyl)(2-(2,3,4-trimethoxyphenyl)cyclopent-1-en-1-yl)methanone (4) of them, four new 1,2-disubstituted cyclopentane derivatives (10-13) with phenyl and benzyl units were synthesized by reactions such as hydrazonation, catalytic hydrogenation and bromination. The obtained compounds 4-13 were examined for their in vitro inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. All compounds 4-13 showed inhibition at nanomolar level with Ki values in the range of 45.53 ± 7.35-631.96 ± 18.88 nM for AChE, 84.30 ± 9.92-622.10 ± 35.14 nM for BChE, and 25.47 ± 4.46-48.87 ± 7.33 for α-Glu. In silico molecular docking studies of the potent compounds were performed in the active sites of AChE (PDB: 1E66), BChE (PDB: 1P0I), and α-glucosidase (PDB: 5ZCC) to compare the effect of bromine atom on the inhibition mechanism. The optimized molecular structures, HOMO-LUMO energies and molecular electrostatic potential maps for the compounds were calculated by using density functional theory with B3LYP/6-31 + G(d,p).
摘要：
根据文献由己二酰氯与1,2,3-三甲氧基苯的反应制备六种已知产物(4-9)。从它们的（2,3,4-三甲氧基苯基）（2-（2,3,4-三甲氧基苯基）环戊-1-烯-1-基）甲酮（4），通过肼化等反应合成了四个新的具有苯基和苄基单元的1,2-二取代环戊烷衍生物（10-13），催化氢化和溴化。检测所得化合物4-13对乙酰胆碱酯酶(AChE)的体外抑制活性,丁酰胆碱酯酶（BChE）和α-葡萄糖苷酶。所有化合物4-13在纳摩尔水平显示抑制,对于AChE,Ki值在45.53±7.35-631.96±18.88nM的范围内,对于BChE，84.30±9.92-622.10±35.14nM，α-Glu为25.47±4.46-48.87±7.33。在AChE（PDB：1E66）的活性位点进行了有效化合物的计算机分子对接研究，BChE(PDB:1P0I),和α-葡萄糖苷酶(PDB:5ZCC)比较溴原子对抑制机制的影响。优化的分子结构,通过使用密度泛函理论与B3LYP/6-31G（d，P).
