背景:反式-[Cu(quin)2(EtOH)2],一种新的铜(II)络合物,使用各种计算技术来探索其在药理学应用中的生物学作用。
方法:计算方法包括密度泛函理论(DFT),ADMET和分子对接。
结果:优化的几何参数表明,含有Cu离子和喹啉酸盐配体的平面被确认为接近平面。DFT研究结果表明,该配合物具有稳定的结构,具有3.88eV的中等带隙。最高占据分子轨道(HOMO)和最低未占据分子轨道(LUMO)分析显示平面表面分子内电荷转移来自其供体位点,在中心,到它的两端,而不是垂直平面。在分子静电势(MEP)图中观察到氧离子周围的两个富电子区域,这被认为是分子键合和与靶蛋白相互作用的位点。确定药物相似度和药代动力学参数以提供对所研究化合物的安全水平的了解。ADMET(吸收,分布,新陈代谢,排泄,和毒性)结果显示良好的药理特征,口服生物利用度高,毒性风险低。通过将铜络合物拟合到蜡状芽孢杆菌的靶蛋白的活性位点进行分子对接研究,金黄色葡萄球菌,和大肠杆菌。标题复合物在蜡状芽孢杆菌的抑制区内具有最强的抗真菌作用,具有〜9.83kcal/mol的强结合亲和力。此外,与最近报道的其他Cu配合物相比,对金黄色葡萄球菌的活性最大(-6.65kcal/mol)在筛选的参考范围内。对接研究涉及对大肠杆菌细菌的适度抑制活性。
结论:研究结果强调了该化合物的生物学活性,并将其确定为细菌蜡样芽孢杆菌和金黄色葡萄球菌的可能治疗药物。
Trans-[Cu (quin)2(EtOH)2], a new copper (II) complex, was characterized using a variety of computational techniques to explore its biological role in pharmacological applications.
The computational methods included density functional theory (DFT), ADMET and molecular docking.
The optimized geometrical parameters revealed that the plane containing the Cu ion and the Quinaldinate ligands was confirmed to be nearly planar. DFT findings suggest that the complex has a stable structure with a moderate band gap of 3.88 eV. Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) analysis revealed a planar surface intramolecular charge transfer from its donor sites, in the center, to its ends instead of the vertical plane. Two electron-rich regions were observed around the oxygen ions in the molecular electrostatic potential (MEP) map, which were expected to be the sites of molecular bonding and interactions with target proteins. Drug-likeness and pharmacokinetics parameters were determined to provide insight into the safety level of the studied compound. The ADMET (absorption, distribution, metabolism, excretion, and toxicity) results showed favorable pharmacological features, as evidenced by a high oral bioavailability and a low risk of toxicity. A molecular docking study was performed by fitting the copper complex into the active sites of target proteins for Bacillus cereus, Staphylococcus aureus, and Escherichia coli bacteria. The title complex had the strongest antifungal effect within the inhibitory zone of B. cereus with a strong binding affinity of -9.83 kcal/mol. Also, maximum activity was exhibited against S.aureus (-6.65 kcal/mol) compared to the other recently reported Cu complexes within the limits of the screened references. Docking studies implicated modest inhibitory activity against E. coli bacteria.
The findings highlighted the compound\'s biological activities and identified it as a possible treatment drug for the bacteria B. cereus and S. aureus.