Ramadan Ramadan M, El-Shalakany Hadeel H, Sayed Mostafa A
Chemistry Department, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt.
Sci Rep. 2025 May 27;15(1):18546. doi: 10.1038/s41598-025-03147-9.
Ruthenium(III) complexes with Schiff base ligands bearing diverse functional groups remain extensively underexplored, despite their promising potential in therapeutic applications. To address this gap, we designed and synthesized a new series of mononuclear octahedral Ru(III) complexes with the general formula [RuL], where L, L, and L are deprotonated Schiff bases derived from functionalized aromatic precursors. These complexes were characterized through a suite of physicochemical and spectroscopic techniques, including FT-IR, H-NMR, UV-Vis spectroscopy, mass spectrometry, TGA, and elemental analysis, to confirm their structural features and coordination environment. To complement experimental findings, density functional theory (DFT/B3LYP) calculations were conducted, revealing stable, distorted octahedral geometries and supporting the proposed molecular configurations. Building upon the structural insights, we evaluated the biological activity of the complexes through in vitro cytotoxicity assays against HCT-116 (colorectal), MCF-7 (breast), and HepG2 (liver) cancer cell lines. Among them, RuL exhibited the most potent activity against HCT-116 (IC₅₀ = 4.97 µg/mL), comparable to the standard drug Vinblastine. Finally, molecular docking simulations were employed to investigate the interaction of these complexes with key biological targets from Escherichia coli (PDB IDs: 4BJP and 1BNA), offering further insights into their potential modes of action. Together, these results demonstrate the importance of ligand design in tuning the coordination behavior and bioactivity of ruthenium complexes, highlighting their promise in anticancer and antimicrobial drug development.
尽管含不同官能团的席夫碱配体钌（III）配合物在治疗应用中具有广阔前景，但仍未得到充分研究。为填补这一空白，我们设计并合成了一系列通式为[RuL]的新型单核八面体钌（III）配合物，其中L、L和L是由功能化芳香前体衍生而来的去质子化席夫碱。通过一系列物理化学和光谱技术对这些配合物进行了表征，包括傅里叶变换红外光谱（FT-IR）、氢核磁共振（H-NMR）、紫外可见光谱（UV-Vis）、质谱、热重分析（TGA）和元素分析，以确认其结构特征和配位环境。为补充实验结果，进行了密度泛函理论（DFT/B3LYP）计算，揭示了稳定的扭曲八面体几何结构，并支持所提出的分子构型。基于这些结构见解，我们通过对HCT-116（结肠）、MCF-7（乳腺）和HepG2（肝脏）癌细胞系的体外细胞毒性试验评估了配合物的生物活性。其中，RuL对HCT-116表现出最强的活性（IC₅₀ = 4.97 μg/mL），与标准药物长春碱相当。最后，采用分子对接模拟研究了这些配合物与大肠杆菌关键生物靶点（PDB ID：4BJP和1BNA）的相互作用，进一步深入了解了它们潜在的作用模式。总之，这些结果证明了配体设计在调节钌配合物的配位行为和生物活性方面的重要性，突出了它们在抗癌和抗菌药物开发中的前景。
