Department of Medicinal Chemistry & Fine Organic Synthesis, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, Russia.
Scientific Center for Innovative Drugs, Volgograd State Medical University, 39 Novorossiyskaya Street, 400087 Volgograd, Russia.
Int J Mol Sci. 2021 Dec 15;22(24):13468. doi: 10.3390/ijms222413468.
A series of bifunctional Ru(III) complexes with lonidamine-modified ligands (lonidamine is a selective inhibitor of aerobic glycolysis in cancer cells) was described. Redox properties of Ru(III) complexes were characterized by cyclic voltammetry. An easy reduction suggested a perspective for these agents as their whole mechanism of action seems to be based on activation by metal atom reduction. New compounds demonstrated a more pronounced antiproliferative potency than the parental drug; individual new agents were more cytotoxic than cisplatin. Stability studies showed an increase in the stability of complexes along with the linker length. A similar trend was noted for antiproliferative activity, cellular uptake, apoptosis induction, and thioredoxin reductase inhibition. Finally, at concentrations that did not alter water solubility, the selected new complex evoked no acute toxicity in Balb/c mice.
一系列带有 lonidamine 修饰配体的双功能 Ru(III) 配合物（lonidamine 是癌细胞有氧糖酵解的选择性抑制剂）被描述。通过循环伏安法对 Ru(III) 配合物的氧化还原性质进行了表征。容易还原表明这些药物具有前景，因为它们的整个作用机制似乎基于金属原子还原的激活。新化合物比母体药物表现出更明显的抗增殖活性；个别新化合物比顺铂更具细胞毒性。稳定性研究表明，随着连接体长度的增加，配合物的稳定性增加。类似的趋势也存在于抗增殖活性、细胞摄取、细胞凋亡诱导和硫氧还蛋白还原酶抑制中。最后，在所不改变水溶解度的浓度下，所选的新型配合物在 Balb/c 小鼠中未引起急性毒性。
