Three new ruthenium(II) complexes were synthesized from different substituted isothiazole ligands 5-(methylamino)-3-pyrrolidine-1-ylisothiazole-4-carbonitrile (1), 5-(methylamino)-3-(4-methylpiperazine-1-yl)isothiazole-4-carbonitrile (2) and 5-(methylamino)-3-morpholine-4-ylisothiazole-4-carbonitrile (3): [Ru(η⁶-p-cymene)Cl₂(L1)]·H₂O (4), [Ru(η⁶-p-cymene)Cl₂(L2)] (5) and [Ru(η⁶-p-cymene)Cl₂(L3)] (6). All complexes were characterized by IR, UV–Vis, NMR spectroscopy, and elemental analysis. The molecular structures of all ligands and complexes 4 and 6 were determined by an X-ray. The results of the interactions of CT-DNA (calf thymus deoxyribonucleic acid) and HSA (human serum albumin) with ruthenium (II) complexes reveal that complex 4 binds well to CT-DNA and HSA. Kinetic and thermodynamic parameters for the reaction between complex and HSA confirmed the associative mode of interaction. The results of Quantum mechanics (QM) modelling and docking experiments toward DNA dodecamer and HSA support the strongest binding of the complex 4 to DNA major groove, as well as its binding to IIa domain of HSA with the lowest ΔG energy, which agrees with the solution studies. The modified GOLD docking results are indicative for Ru(p-cymene)LCl··(HSA··GLU292) binding and GOLD/MOPAC(QM) docking/modelling of DNA/Ligand (Ru(II)-N(7)dG7) covalent binding. The cytotoxic activity of compounds was evaluated by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Neither of the tested compounds shows activity against a healthy MRC-5 cell line while the MCF-7 cell line is the most sensitive to all. Compounds 3, 4 and 5 were about two times more active than cisplatin, while the antiproliferative activity of 6 was almost the same as with cisplatin. Flow cytometry analysis showed the apoptotic death of the cells with a cell cycle arrest in the subG1 phase.

从不同的取代异噻唑配体5-（甲基氨基）-3-吡咯烷-1-基异噻唑-4-腈（1），5-（甲基氨基）-3-（4-甲基哌嗪-1- ）合成了三种新的钌（II）配合物基）异噻唑-4-甲腈（2）和5-（甲基氨基）-3-吗啉-4- ylisothiazole -4-甲腈（3）：[茹（η ⁶ - p -cymene）氯₂（L 1）]· ħ ₂ O（4），的[Ru（η ⁶ - p -cymene）氯₂（L 2）]（5）和[茹（η ⁶ - p -cymene）氯₂（L 3）]（6）。所有复合物均通过IR，UV-Vis，NMR光谱和元素分析进行​​表征。通过X射线测定所有配体以及配合物4和6的分子结构。CT-DNA（小牛胸腺脱氧核糖核酸）和HSA（人血清白蛋白）与钌（II）配合物相互作用的结果表明，配合物4与CT-DNA和HSA结合良好。配合物与HSA之间反应的动力学和热力学参数证实了相互作用的缔合模式。量子力学（QM）建模和对DNA dodecamer和HSA的对接实验的结果支持了复合物4的最强结合DNA的主要凹槽，以及与具有最低ΔG能量的HSA IIa结构域的结合，这与溶液研究一致。修改后的GOLD对接结果表明Ru（p- cymene）LCl··（HSA··GLU292）结合和DNA /配体（Ru（II）-N（7）dG7）的GOLD / MOPAC（QM）对接/建模。共价结合。通过MTT（3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2H-溴化四唑）测定来评估化合物的细胞毒性活性。两种测试化合物均未显示出针对健康的MRC-5细胞系的活性，而MCF-7细胞系对所有人均最敏感。化合物3，4和5分别为约两倍比顺铂更活跃，而的抗增殖活性6与顺铂几乎相同。流式细胞仪分析显示细胞凋亡死亡，并且细胞周期停滞在subG1期。