Design, Synthesis, DNA/HSA Binding, and Cytotoxic Activity of Half-Sandwich Ru(II)-Arene Complexes Containing Triarylamine–Thiosemicarbazone Hybrids

Organoruthenium complexes are potent alternatives for platinum-based complexes because of their superior anticancer activity. In this investigation, a series of new Ru­(II)-arene complexes with triarylamine–thiosemicarbazone hybrid ligands with higher anticancer activity than cisplatin are reported. The molecular structure of the ligands and complexes was confirmed spectroscopically and supported by single-crystal X-ray crystallography. These complexes adopted a three-leg piano stool geometry. All the Ru­(II)-arene complexes were systematically investigated for their in vitro cytotoxicity against human cervical (HeLa S3), lung (A549) cancer, and human normal lung (IMR-90) cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Interestingly, a pyrrolidine-attached Ru­(II)-benzene complex exhibited superior activity against cancer cells with low IC50 values, and colony formation study showed complete inhibition at 5 and 10 μM concentration. Furthermore, morphological changes assessed by acridine orange and propidium iodide staining revealed that the cell death occurred by apoptosis. In addition, the interaction between synthesized Ru­(II)-arene complexes and DNA/protein was explored by absorption and emission spectroscopy methods. These synthesized new organoruthenium complexes can be used for developing new metal-based anticancer drugs.

有机钌配合物凭借其优异的抗癌活性，成为铂类配合物极具潜力的替代方案。本研究报道了一系列基于三芳胺-氨基硫脲杂合配体的新型钌(II)-芳烃（Ru(II)-arene）配合物，其抗癌活性优于顺铂。通过光谱学手段确证了配体及配合物的分子结构，并通过单晶X射线衍射（single-crystal X-ray crystallography）得到验证。此类配合物均呈现三足钢琴凳式空间构型。本研究采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）比色法，系统评价了所有钌(II)-芳烃配合物对人宫颈癌细胞（HeLa S3）、肺癌细胞（A549）以及正常人肺细胞（IMR-90）的体外细胞毒性。值得注意的是，一种连有吡咯烷基的钌(II)-苯配合物对癌细胞展现出优异的杀伤活性，其半数抑制浓度（IC50）极低；集落形成实验结果显示，在5 μM和10 μM浓度下即可完全抑制癌细胞集落形成。此外，通过吖啶橙（acridine orange）与碘化丙啶（propidium iodide）染色对细胞形态变化进行检测，结果表明该配合物通过凋亡途径诱导癌细胞死亡。另外，本研究还通过吸收光谱与发射光谱法，探究了合成得到的钌(II)-芳烃配合物与DNA/蛋白质的相互作用。此类新型合成有机钌配合物可用于开发新一代金属基抗癌药物。