Alghabban Hadel M, Nass Nada M, Alaeq Rana Abdulrahim, Alghabban Dema M, Alrahimi Jehan, Jambi Rana Jamalaldin, Abd El-Karim Abeer Taha, Mansour M S A, Fayek Ayman A, El-Sherif Ahmed A
Department of Basic Medical Sciences, College of Medicine, Taibah University, Madinah, Kingdom of Saudi Arabia.
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, Jidda, Kingdom of Saudi Arabia.
Med Oncol. 2025 Jul 16;42(8):336. doi: 10.1007/s12032-025-02872-5.
This study reports the synthesis and biomedical evaluation of novel ternary metal complexes based on a tridentate Schiff base ligand (CHPT) and 1,10-phenanthroline (PHEN) as a co-ligand. The ligand, (Z)-2-((E)-1-(2-(4-chlorophenyl)hydrazineylidene)propan-2-ylidene)-N-phenylhydrazine-1-carbothioamide, was used to construct Fe(III), Co(II), and Cu(II) complexes. The complexes were characterized using elemental analysis, FT-IR, UV-Vis, mass spectroscopy, and conductivity measurements. All complexes exhibited distorted octahedral geometries. Density Functional Theory (DFT) calculations (B3LYP/LANL2DZ) provided insight into electronic properties, including HOMO-LUMO gaps, chemical reactivity, and electrostatic potential. Biological screening revealed significant antimicrobial activity, with the Cu(II) complex displaying the highest potency against Gram-positive and Gram-negative bacteria, as well as Candida albicans. The Cu(II) complex also exhibited strong anti-H. pylori activity and superior anticancer efficacy against MCF-7 breast cancer cells (IC₅₀ = 10.5 µg/mL), while maintaining low toxicity toward normal VERO cells. It also showed promising activity against K-562 leukemia cells (IC₅₀ = 287.19 µg/mL). Molecular docking studies supported the multi-target potential of the Cu(II) complex by confirming stable binding with key therapeutic targets such as FLT3 kinase, BCL-2, IDH2 R140. Furthermore, Swiss ADME predictions confirmed that the Cu(II) complex possesses favorable drug-likeness, bioavailability, and low CYP-mediated interaction risks, supporting its potential as a multi-target therapeutic agent.
本研究报告了基于三齿席夫碱配体（CHPT）和作为共配体的1,10-菲咯啉（PHEN）的新型三元金属配合物的合成及生物医学评价。配体（Z）-2-（（E）-1-（2-（4-氯苯基）肼叉）丙烷-2-亚基）-N-苯基肼-1-碳硫酰胺用于构建铁（III）、钴（II）和铜（II）配合物。通过元素分析、傅里叶变换红外光谱（FT-IR）、紫外-可见光谱（UV-Vis）、质谱和电导率测量对配合物进行了表征。所有配合物均呈现扭曲的八面体几何构型。密度泛函理论（DFT）计算（B3LYP/LANL2DZ）深入了解了电子性质，包括最高占据分子轨道-最低未占据分子轨道（HOMO-LUMO）能隙、化学反应性和静电势。生物筛选显示出显著的抗菌活性，其中铜（II）配合物对革兰氏阳性菌、革兰氏阴性菌以及白色念珠菌表现出最高的效力。铜（II）配合物还表现出较强的抗幽门螺杆菌活性以及对MCF-7乳腺癌细胞的优异抗癌疗效（半数抑制浓度（IC₅₀）=10.5 μg/mL），同时对正常VERO细胞保持低毒性。它对K-562白血病细胞也显示出有前景的活性（IC₅₀=287.19 μg/mL）。分子对接研究通过证实与关键治疗靶点如FMS样酪氨酸激酶3（FLT3）激酶、B细胞淋巴瘤-2（BCL-2）、异柠檬酸脱氢酶2（IDH2）R140的稳定结合，支持了铜（II）配合物的多靶点潜力。此外，瑞士药物代谢和药物相互作用预测（Swiss ADME）证实铜（II）配合物具有良好的类药性、生物利用度以及低细胞色素P450（CYP）介导的相互作用风险，支持其作为多靶点治疗剂的潜力。
