Department of Inorganic Chemistry, Faculty of Science, Palacky University in Olomouc, 17. listopadu 12, 77146 Olomouc, Czech Republic.
Department of Biophysics, Faculty of Science, Palacky University in Olomouc, Slechtitelu 27, 78371 Olomouc, Czech Republic.
Dalton Trans. 2021 Jun 15;50(23):8017-8028. doi: 10.1039/d1dt00466b.
Complexes [Ru(η6-pcym)(bpydca)Cl]PF6 (Rudca) and [Ir(η5-Cp*)(bpydca)Cl]PF6 (Irdca) were developed as model compounds for the investigation of multi-targeted ester-functionalized half-sandwich ruthenium(ii) and iridium(iii) complexes; pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), bpydca = 2,2'-bipyridine-4,4'-diyldimethanediyl bis(dichloroacetate), Cp* = pentamethylcyclopentadienyl. Aiming to understand the in-solution behaviour of these first-in-class complexes containing the pyruvate dehydrogenase kinase inhibitor dichloroacetate (dca) as the terminal bioactive substituent, several experiments were performed under aqueous conditions for Rudca and Irdca, as well as for compounds [Ru(η6-pcym)(bpyOH)Cl]PF6 (RuOH) and [Ir(η5-Cp*)(bpyOH)Cl]PF6 (IrOH), and acetyl analogues [Ru(η6-pcym)(bpyac)Cl]PF6 (Ruac) and [Ir(η5-Cp*)(bpyac)Cl]PF6 (Irac) bearing a different (biologically inactive) terminal substituent; bpyOH = 2,2'-bipyridine-4,4'-diyldimethanol, bpyac = 2,2'-bipyridine-4,4'-diyldimethanediyl diacetate. The experiments were also conducted in the presence of porcine liver esterase (PLE). All the six complexes were characterized by relevant techniques (e.g., NMR and mass spectrometry), including a single-crystal X-ray analysis of complexes Rudca, Ruac, RuOH and IrOH. Although designed as model compounds, Rudca, Irdca, RuOH and IrOH were also screened for their antiproliferative activity in four human cancer cell lines (HCT116 colon carcinoma, MDA-MB-231 and MCF-7 breast adenocarcinomas, DU145 prostate carcinoma), where the tested complexes did not show any effect (IC50 > 100 μM).
开发了配合物[Ru(η6-pcym)(bpydca)Cl]PF6（Rudca）和[Ir(η5-Cp*)(bpydca)Cl]PF6（Irdca）作为多靶酯功能化半夹心钌（ii）和铱（iii）配合物的模型化合物；pcym = 1-甲基-4-（异丙基）苯（对伞花烃），bpydca = 2,2'-联吡啶-4,4'-二亚甲基双（二氯乙酸酯），Cp* = 五甲基环戊二烯基。为了了解含有丙酮酸脱氢酶激酶抑制剂二氯乙酸（dca）作为末端生物活性取代基的这些首例复合物在溶液中的行为，在Rudca 和 Irdca 以及配合物[Ru(η6-pcym)(bpyOH)Cl]PF6（RuOH）和[Ir(η5-Cp*)(bpyOH)Cl]PF6（IrOH）以及具有不同（生物惰性）末端取代基的乙酰类似物[Ru(η6-pcym)(bpyac)Cl]PF6（Ruac）和[Ir(η5-Cp*)(bpyac)Cl]PF6（Irac）的水相条件下进行了几项实验；bpyOH = 2,2'-联吡啶-4,4'-二醇，bpyac = 2,2'-联吡啶-4,4'-二亚甲基二乙酸酯。实验还在猪肝酯酶（PLE）存在下进行。所有六种配合物均通过相关技术（例如 NMR 和质谱）进行了表征，包括配合物 Rudca、Ruac、RuOH 和 IrOH 的单晶 X 射线分析。尽管被设计为模型化合物，但 Rudca、Irdca、RuOH 和 IrOH 也在四种人类癌细胞系（HCT116 结肠癌细胞、MDA-MB-231 和 MCF-7 乳腺癌、DU145 前列腺癌细胞）中进行了抗增殖活性筛选，其中测试的配合物没有显示出任何效果（IC50 > 100 μM）。
