Four new ruthenium(II) coordination compounds bearing coumarin derivatives as anticancer agents

IF 2.4 3区化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR

Polyhedron Pub Date : 2024-08-20 DOI:10.1016/j.poly.2024.117192

Qi-Pin Qin , Xiao-Feng Zhou , Ling-Qi Du , Yue-Jiao Liang , Jin-Yuan Cai , Song Sun , Yan Yang

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Abstract

Toward the development of effective metal-based coordination drugs for the treatment of cisplatin-resistant cancers, we report four new ruthenium(II) coordination compounds, namely, [RuCl₂(yc1)₂(DMSO)₂] (QY1), [RuCl₂(yc2)₂(DMSO)₂] (QY2), [RuCl₂(yc3)₂(DMSO)₂] (QY3), and [RuCl₂(yc4)₂(DMSO)₂]·1.25H₂O (QY4), which contain 3-pyridin-2-yl-chromen-2-one (yc1), 8-methyl-3-pyridin-2-yl-chromen-2-one (yc2), 7-methoxy-3-pyridin-2-yl-chromen-2-one (yc3), and 2-pyridin-2-yl-benzo[f]chromen-3-one (yc4) ligands, respectively. Complex QY4 possessing a more extended planar yc4 ligand showed the highest cytotoxicity against cisplatin-resistant A549/DDP lung cancer cells (R9LC), yielding a remarkably low micromolar IC₅₀ value of 5.02 ± 0.14 μM and low toxicity against embryonic kidney HEK293 (e293) normal cells under equal conditions (IC₅₀ = 88.04 ± 1.03 μM). Notably, QY4 exhibited higher cytotoxicity than QY1–QY3, yc1–yc4, and cisplatin. QY4 and QY1, especially QY4, induced R9LC apoptosis via mitochondrial dysfunction, which involved mitochondrial membrane potential (MP) damage, ROS/Ca²⁺ activation, and apoptosis protein up-regulation. Thus, these coumarin ruthenium(II) coordination compounds are promising mitochondria-targeting anticancer agents.

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含香豆素衍生物的四种新型钌（II）配位化合物作为抗癌剂

为了开发治疗顺铂耐药性癌症的有效金属配位药物，我们报告了四种新的钌(II)配位化合物，即[RuCl2(yc1)2(DMSO)2](QY1)、[RuCl2(yc2)2(DMSO)2](QY2)、[RuCl2(yc3)2(DMSO)2](QY3)和[RuCl2(yc4)2(DMSO)2]-1。25H2O（QY4），它们分别含有 3-吡啶-2-基-苯并吡喃-2-酮（yc1）、8-甲基-3-吡啶-2-基-苯并吡喃-2-酮（yc2）、7-甲氧基-3-吡啶-2-基-苯并吡喃-2-酮（yc3）和 2-吡啶-2-基-苯并[f]苯并吡喃-3-酮（yc4）配体。复合物 QY4 具有更长的平面 yc4 配体，对顺铂耐药的 A549/DDP 肺癌细胞（R9LC）具有最高的细胞毒性，微摩尔 IC50 值低至 5.02 ± 0.14 μM，在同等条件下对胚胎肾 HEK293（e293）正常细胞的毒性较低（IC50 = 88.04 ± 1.03 μM）。值得注意的是，QY4 的细胞毒性高于 QY1-QY3、yc1-yc4 和顺铂。QY4 和 QY1，尤其是 QY4，通过线粒体功能障碍诱导 R9LC 细胞凋亡，其中包括线粒体膜电位（MP）损伤、ROS/Ca2+ 激活和凋亡蛋白上调。因此，这些香豆素钌（II）配位化合物是很有前景的线粒体靶向抗癌剂。

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来源期刊

Polyhedron 化学-晶体学

CiteScore

4.90

自引率

7.70%

发文量

515

审稿时长

2 months

期刊介绍： Polyhedron publishes original, fundamental, experimental and theoretical work of the highest quality in all the major areas of inorganic chemistry. This includes synthetic chemistry, coordination chemistry, organometallic chemistry, bioinorganic chemistry, and solid-state and materials chemistry. Papers should be significant pieces of work, and all new compounds must be appropriately characterized. The inclusion of single-crystal X-ray structural data is strongly encouraged, but papers reporting only the X-ray structure determination of a single compound will usually not be considered. Papers on solid-state or materials chemistry will be expected to have a significant molecular chemistry component (such as the synthesis and characterization of the molecular precursors and/or a systematic study of the use of different precursors or reaction conditions) or demonstrate a cutting-edge application (for example inorganic materials for energy applications). Papers dealing only with stability constants are not considered.