Conformational Analysis, Spectroscopic Insights, Chemical Descriptors, ELF, LOL and Molecular Docking Studies of Potential Pyrimidine Derivative with Biological Activities

The geometry, frontier molecular orbitals, chemical reactivity, vibrational, NBO analysis and molecular docking simulations of Ethyl −2-(4-propoxybenzylidene)-7-methyl-3-oxo-5-(4-benzyloxy phenyl)-2,3-dihydro-5<i>H</i>-[1, 3]thiazolo[3,2-a]pyrimidine-6-carboxylate (EBPC) have been extensively studied and discussed on DFT calculations. The stable structural conformational analysis has been achieved using potential energy scan for different rotable bonds. The lowest energy of the conformer was obtained from rotation along C2-C3-C26-O27. Electrostatic potential map, UV-Vis and chemical descriptors and drug-likeness properties are analyzed. Localization function and local orbital locator functions are also discussed. Charge delocalization patterns and second order perturbation energies of the most interacting natural bond orbitals have also been computed and predicted. Most of covalent region is in between blue circles around sulfur and few carbon, nitrogen atoms show that the electron depletion region. Docking binding affinities and the formation of a good number of hydrogen bonds suggests that the title compound appears to be a promising drug for the selected inhibitors.

本研究基于密度泛函理论（Density Functional Theory, DFT）计算，对乙基-2-(4-丙氧基苯亚甲基)-7-甲基-3-氧代-5-(4-苄氧基苯基)-2,3-二氢-5<i>H</i>-[1,3]thiazolo[3,2-a]嘧啶-6-羧酸酯（Ethyl −2-(4-propoxybenzylidene)-7-methyl-3-oxo-5-(4-benzyloxy phenyl)-2,3-dihydro-5<i>H</i>-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate，简称EBPC）的几何结构、前线分子轨道、化学反应活性、振动特性、自然键轨道（Natural Bond Orbital, NBO）分析及分子对接模拟进行了广泛研究与讨论。通过对不同可旋转键开展势能面扫描完成该化合物的稳定构象分析，其中沿C2-C3-C26-O27键旋转得到的构象拥有最低能量。本研究还对其静电势图、紫外-可见（UV-Vis）吸收光谱、化学描述符及药物相似性性质进行了分析，探讨了定域化函数与定域轨道定位器（Local Orbital Locator, LOL）函数的相关特性，同时计算并预测了电荷离域模式以及相互作用最强的自然键轨道的二阶微扰能。硫原子周围的蓝色圆形区域为主要共价作用区，少量碳、氮原子所在区域则呈现电子耗竭特征。分子对接结合能以及大量氢键的形成表明，该标题化合物EBPC对于所选靶点抑制剂而言，是一种极具开发潜力的候选药物。