Centre for Organometallic Chemistry, School of Chemistry, Bharathidasan University, Tiruchirappalli-620024, India.
Dalton Trans. 2024 Aug 13;53(32):13469-13477. doi: 10.1039/d4dt01845a.
Efforts in researching the efficient anti-tumor properties of three novel arene ruthenium(II) complexes incorporating thiophene-based aroylhydrazone ligands have been undertaken. The complexes' elemental composition was [(--cymene)Ru(L)Cl]. They were comprehensively characterized through elemental and spectroscopic analyses (FT-IR, UV-vis, NMR, and HR-MS). Single crystal X-ray diffraction studies revealed a pseudo-octahedral geometry with bidentate coordination of the ligands in a representative complex. The assessment of the complexes' cancer cell growth inhibition was conducted using the MTT assay against A549 (human lung carcinoma), HeLa (human cervical carcinoma), HuH-7 (hepatocellular carcinoma), and NIH-3T3 (mouse fibroblast non-cancerous cell line). Results indicated significant cytotoxicity across all cancer cell lines, with IC concentrations of complex 2 being 6.8 μM for A549, 11.6 μM for HeLa, and 9.4 μM for HuH-7, compared to cisplatin with IC values of 18.9 μM, 17.68 μM, and 24 μM respectively. Notably, complex 2 demonstrated particularly promising cytotoxicity against all tested cancerous cell lines. Fluorescent staining analysis such as acridine orange/ethidium bromide (AO-EB) and HOECHST 33342 revealed cell death mechanisms involving membrane disintegration and nuclear condensation following treatment with complex 2. Further studies were conducted to measure reactive oxygen species (ROS) levels using the dichlorodihydrofluorescein diacetate (DCFH-DA) assay, and mitochondrial membrane potential (MMP) was assessed using the JC-1 dye assay. These studies demonstrated that complex 2 increased ROS levels, decreased membrane potential, and promoted mitochondrial dysfunction-mediated cell death pathways. Additionally, flow cytometry analysis, utilizing dual staining of Annexin V-FITC and propidium iodide (PI), was employed to quantitatively study apoptosis induction.
研究三种新型含噻吩基甲酰腙配体的芳基钌(II)配合物的高效抗肿瘤特性的工作已经开展。这些配合物的元素组成为[(--cymene)Ru(L)Cl]。通过元素分析和光谱分析（FT-IR、UV-vis、NMR 和 HR-MS）对它们进行了全面的表征。单晶 X 射线衍射研究表明，在一个代表性的配合物中，配体呈双齿配位，具有拟八面体几何形状。通过 MTT 测定法评估了配合物对 A549（人肺癌）、HeLa（人宫颈癌）、HuH-7（肝癌）和 NIH-3T3（小鼠成纤维细胞非癌细胞系）的癌细胞生长抑制作用。结果表明，所有癌细胞系均具有显著的细胞毒性，其中配合物 2 对 A549 的 IC 浓度为 6.8 μM，对 HeLa 的 IC 浓度为 11.6 μM，对 HuH-7 的 IC 浓度为 9.4 μM，而顺铂的 IC 值分别为 18.9 μM、17.68 μM 和 24 μM。值得注意的是，配合物 2 对所有测试的癌细胞系均表现出特别有前途的细胞毒性。吖啶橙/溴化乙锭（AO-EB）和 HOECHST 33342 等荧光染色分析表明，细胞死亡机制涉及细胞膜破裂和细胞核浓缩，这是在用配合物 2 处理后发生的。进一步的研究通过二氯二氢荧光素二乙酸酯（DCFH-DA）测定法来测量活性氧（ROS）水平，并通过 JC-1 染料测定法评估线粒体膜电位（MMP）。这些研究表明，配合物 2 增加了 ROS 水平，降低了膜电位，并促进了线粒体功能障碍介导的细胞死亡途径。此外，还使用 Annexin V-FITC 和碘化丙啶（PI）双重染色的流式细胞术分析，定量研究了凋亡诱导。
