Department of Chemistry, National Institute of Technology, Tiruchirappalli, 620015, Tamil Nadu, India.
DRDO-BU Centre for Life Sciences, Bharathiar University Campus, Coimbatore, 641046, Tamil Nadu, India.
Chemistry. 2021 May 6;27(26):7418-7433. doi: 10.1002/chem.202004954. Epub 2021 Mar 12.
Fourteen new Ru -arene (p-cymene/benzene) complexes (C1-C14) have been synthesized by varying the N-terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure-activity relationships of the Ru-p-cymene and Ru-benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR-32 cancer cells, with C5 (Ru-p-cymene complex containing C H (CH ) as N-terminal substituent) and C13 (Ru-benzene complex containing C H (CF ) as N-terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim-1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells.
十四种新型钌-芳烃（对伞花烃/苯）配合物（C1-C14）已通过改变呋喃甲酰基硫脲配体的 N-端取代基合成，并通过分析和光谱技术进行了满意的表征。静电势能图预测取代基的电子效应主要是局部的，对不稳定的氯配体有一定的影响。Ru-p-cymene 和 Ru-benzene 配合物的结构-活性关系呈现出相反的趋势。所有配合物对 IMR-32 癌细胞都具有很高的毒性，其中 C5（含 N-端取代基 C H (CH )的 Ru-p-cymene 配合物）和 C13（含 N-端取代基 C H (CF )的 Ru-benzene 配合物）在各自的配合物组中表现出最高的活性，因此选择它们进行进一步研究。这些配合物在水溶液中表现出不同的行为，也被发现可以催化氧化谷胱甘肽。它们还通过细胞凋亡和细胞周期阻滞促进细胞死亡。此外，这些配合物与受体 Pim-1 激酶和血管内皮生长因子受体 2 具有良好的结合能力，这些受体通常在癌细胞中过度表达。
