Alam Mahboob, Lee Dong-Ung
Division of Bioscience, Dongguk University, Gyeongju 780-714, Republic of Korea.
Division of Bioscience, Dongguk University, Gyeongju 780-714, Republic of Korea.
Comput Biol Chem. 2016 Oct;64:185-201. doi: 10.1016/j.compbiolchem.2016.06.006. Epub 2016 Jun 24.
The biologically relevant molecule; 2-(thiophen-2-yl)-2,3-dihydro-1H-perimidine was synthesized and characterized by FT-IR, UV, H and C NMR, MS, CHN microanalysis, X-ray crystallography as well as by theoretical, B3LYP/6-311++G(d,p), calculations. The vibrational bands appearing in the FT-IR were assigned with great accuracy using animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural charges have been presented at the same level of theory. The theoretical results are found in good correlation with the experimental data obtained from the various spectral techniques. Moreover, the Hirshfeld analysis was performed to explore the secondary interactions and associated 2D fingerprint plots. Perimidine molecule displayed promising inhibitory activity against acetylcholinesterase (AChE) as compared to the reference drug, tacrine. Molecular docking was carried out to ascertain the synthesized molecule into the X-ray crystal structures of acetylcholinesterase at the active site to find out the probable binding mode. The results of molecular docking admitted that perimidine may reveal enzyme inhibitor activity.
合成了具有生物学相关性的分子2-(噻吩-2-基)-2,3-二氢-1H-苝啶，并通过傅里叶变换红外光谱(FT-IR)、紫外光谱(UV)、氢核磁共振(H NMR)、碳核磁共振(C NMR)、质谱(MS)、CHN元素微量分析、X射线晶体学以及理论计算（B3LYP/6-311++G(d,p)）对其进行了表征。利用动画模式对FT-IR中出现的振动带进行了高精度的归属。在相同理论水平下给出了分子性质，如最高占据分子轨道(HOMO)-最低未占据分子轨道(LUMO)分析、化学反应性描述符、分子静电势(MEP)映射、偶极矩和自然电荷。理论结果与通过各种光谱技术获得的实验数据具有良好的相关性。此外，进行了 Hirshfeld 分析以探索次级相互作用及相关的二维指纹图谱。与参比药物他克林相比，苝啶分子对乙酰胆碱酯酶(AChE)显示出有前景的抑制活性。进行了分子对接，以确定合成分子在乙酰胆碱酯酶活性位点的X射线晶体结构中的位置，从而找出可能的结合模式。分子对接结果表明苝啶可能具有酶抑制活性。
