Department of Basic Education, Faculty of Education, Burdur Mehmet Akif Ersoy University, 15030, Burdur, Turkey.
Central Research Laboratory Application and Research Center, Isparta University of Applied Sciences, 32200, Isparta, Turkey.
J Mol Model. 2023 Jul 5;29(8):226. doi: 10.1007/s00894-023-05625-1.
Today, the treatment or prevention of cancer, which is one of the most important causes of death, has a very important place. On the other hand, the discovery of new antimicrobial agents is also important because of antibiotic resistance that can occur in humans. For these reasons, in this study, the synthesis, quantum chemical calculations, and in silico studies of a novel azo molecule with high bioactive potential were carried out. In the first step of the synthesis part, (3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline compound, which is the raw material of the drug used in cancer treatments, was synthesized. In the second step, a novel product 2-hydroxy-5-((3-(4-methyl-1H-imidazol-1-yl)-5-trifluoromethyl)phenyl)diazenyl)benzaldehyde (HTB) was obtained as a result of the reaction of salicylaldehyde coupling to this compound. Then, as it was being spectroscopically described, its geometry was optimized. In order to perform quantum chemical calculations, the molecular structure, vibrational spectroscopic data, electronic transition absorption wavelengths, HOMO and LUMO analyses, molecular electrostatic potential (MEP) and potential energy surface (PES) of the molecule were all taken into consideration. Using molecular docking simulations, in silico interactions of the HTB molecule with some anticancer and antibacterial-related proteins were studied. In addition, the ADMET parameters of the HTB were also predicted.
The structure of the synthesized compound was elucidated using H-NMR, C-NMR (APT), F-NMR, FT-IR and UV-vis spectroscopic methods. The optimized geometry, molecular electrostatic potential diagram and vibrational frequencies of the HTB molecule were calculated at the DFT/B3LYP/6-311G(d,p) level. The TD-DFT method was used to calculate HOMOs-LUMOs and electronic transitions, and the GIAO method was used to calculate chemical shift values. It was observed that the experimental spectral data were in good agreement with the theoretical ones. Molecular docking simulations of the HTB molecule using 4 different proteins were investigated. Two of these proteins were involved in simulating anticancer activity and the other two in simulating antibacterial activity. According to molecular docking studies, the binding energies of the complexes formed by the HTB compound with the 4 selected proteins were between -9.6 and -8.7 kcal/mol. HTB showed the best affinity with VEGFR2 protein (PDB ID: 2XIR) and the binding energy of this interaction was found to be -9.6 kcal/mol. The HTB-2XIR interaction was examined with molecular dynamics simulation for 25 ns and it was determined that this complex was stable during this time. In addition, the ADMET parameters of the HTB were also calculated, and from these values, it was determined that the compound has very low toxicity and high oral bioavailability.
如今，癌症的治疗或预防（癌症是最重要的死亡原因之一）具有非常重要的地位。另一方面，由于人类可能会产生抗生素耐药性，因此发现新的抗菌剂也很重要。基于这些原因，在这项研究中，对具有高生物活性潜力的新型偶氮分子进行了合成、量子化学计算和计算机模拟研究。在合成部分的第一步中，合成了（3-（4-甲基-1H-咪唑-1-基）-5-（三氟甲基）苯胺化合物，该化合物是用于癌症治疗的药物的原料。在第二步中，水杨醛偶联到该化合物上，得到了一种新型产物 2-羟基-5-((3-(4-甲基-1H-咪唑-1-基)-5-三氟甲基)苯基)偶氮基)苯甲醛（HTB）。然后，对其进行了光谱描述，优化了其几何形状。为了进行量子化学计算，考虑了分子结构、振动光谱数据、电子跃迁吸收波长、HOMO 和 LUMO 分析、分子静电势（MEP）和势能面（PES）。通过分子对接模拟研究了 HTB 分子与一些抗癌和抗菌相关蛋白的计算机模拟相互作用。此外，还预测了 HTB 的 ADMET 参数。
使用 H-NMR、C-NMR（APT）、F-NMR、FT-IR 和 UV-vis 光谱方法阐明了合成化合物的结构。在 DFT/B3LYP/6-311G(d,p) 水平下计算了 HTB 分子的优化几何形状、分子静电势图和振动频率。使用 TD-DFT 方法计算 HOMO-LUMO 和电子跃迁，使用 GIAO 方法计算化学位移值。观察到实验光谱数据与理论数据吻合良好。使用 4 种不同的蛋白质对 HTB 分子的分子对接模拟进行了研究。其中两种蛋白质参与模拟抗癌活性，另外两种蛋白质参与模拟抗菌活性。根据分子对接研究，HTB 化合物与 4 种选定蛋白质形成的配合物的结合能在-9.6 到-8.7 kcal/mol 之间。HTB 与 VEGFR2 蛋白（PDB ID：2XIR）的亲和力最好，相互作用的结合能为-9.6 kcal/mol。用 25 ns 的分子动力学模拟研究了 HTB-2XIR 相互作用，确定在此期间该复合物稳定。此外，还计算了 HTB 的 ADMET 参数，从这些值可以确定该化合物的毒性非常低，口服生物利用度高。
