Department of Inorganic Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, 51666-14766, Iran.
Department of Microbiology and Immunology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
J Biol Inorg Chem. 2023 Aug;28(5):457-472. doi: 10.1007/s00775-023-02001-5. Epub 2023 May 2.
A novel fluorescent ligand (HLCl⋅1.5CHOH, 1) was synthesized and metal complexes of 1 with Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) were obtained as Mn(HL)Cl (2), Fe(HL)Cl⋅3HO (3), Ni(L)(HL)Cl⋅8HO (4), Cu(HL)Cl⋅4HO (5), Zn(HL)Cl (6), respectively. These compounds were identified by spectroscopic methods, elemental analysis, molar conductivity, and single-crystal X-ray crystallography. According to the crystal structure of 4 nickel (II), center is surrounded by two ligands in a distorted octahedral geometry. The ligand and its complexes are soluble in water and have excellent stability. In vitro anti-proliferative activity of these compounds was evaluated against human breast adenocarcinoma (MCF-7) and human lipo-sarcoma (SW-872) as cancer cells and human fibroblasts (HFF-2) as normal cells by MTT assay. Interestingly, complex 5 exhibited excellent activity against both cancer cells with low IC value 22.18 ± 0.35 μg/mL (35.66 ± 0.56 μM) for SW-872 and 79.41 ± 3.54 μg/mL (127.6 ± 5.69 μM) for MCF-7 among the compounds and in comparison with paclitaxel (PTX) which acts finely. Morphological changes were evaluated by flow cytometry that revealed apoptosis is the main cause of cell death. Likewise, cell cycle studies indicated the cell cycle arrest in the G and S phases for complex 5 against MCF-7 and SW-872 cancer cells, while complex 6 could arrest the MCF-7 and SW-872 cells in G and G phases, respectively. All of the compounds are fluorescent which enabled us to monitor the uptake and intracellular distribution in living human cancer cells by fluorescence microscopy.
一种新型荧光配体（HLCl⋅1.5CHOH，1）被合成，并用 Mn(II)、Fe(III)、Ni(II)、Cu(II) 和 Zn(II) 得到了 1 的金属配合物，分别为 Mn(HL)Cl（2）、Fe(HL)Cl⋅3HO（3）、Ni(L)(HL)Cl⋅8HO（4）、Cu(HL)Cl⋅4HO（5）、Zn(HL)Cl（6）。这些化合物通过光谱方法、元素分析、摩尔电导率和单晶 X 射线晶体学进行了鉴定。根据 4 个镍（II）的晶体结构，中心被两个配体包围在扭曲的八面体几何形状中。配体及其配合物溶于水，具有极好的稳定性。通过 MTT 法评估了这些化合物对人乳腺癌（MCF-7）和人脂肪肉瘤（SW-872）作为癌细胞和人成纤维细胞（HFF-2）作为正常细胞的体外增殖抑制活性。有趣的是，与紫杉醇（PTX）相比，配合物 5 对两种癌细胞均表现出优异的活性，对 SW-872 的 IC 值为 22.18±0.35μg/mL（35.66±0.56μM），对 MCF-7 的 IC 值为 79.41±3.54μg/mL（127.6±5.69μM）。通过流式细胞术评估形态变化，结果表明细胞凋亡是细胞死亡的主要原因。同样，细胞周期研究表明，5 号配合物对 MCF-7 和 SW-872 癌细胞的细胞周期在 G 和 S 期停滞，而 6 号配合物分别使 MCF-7 和 SW-872 细胞停滞在 G 和 G 期。所有的化合物都是荧光的，这使我们能够通过荧光显微镜监测活的人癌细胞中的摄取和细胞内分布。
