Qi-Pin Qin , Xiao-Feng Zhou , Ling-Qi Du , Yue-Jiao Liang , Jin-Yuan Cai , Song Sun , Yan Yang
{"title":"含香豆素衍生物的四种新型钌（II）配位化合物作为抗癌剂","authors":"Qi-Pin Qin , Xiao-Feng Zhou , Ling-Qi Du , Yue-Jiao Liang , Jin-Yuan Cai , Song Sun , Yan Yang","doi":"10.1016/j.poly.2024.117192","DOIUrl":null,"url":null,"abstract":"<div><p>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, [RuCl<sub>2</sub>(yc1)<sub>2</sub>(DMSO)<sub>2</sub>] (<strong>QY1</strong>), [RuCl<sub>2</sub>(yc2)<sub>2</sub>(DMSO)<sub>2</sub>] (<strong>QY2</strong>), [RuCl<sub>2</sub>(yc3)<sub>2</sub>(DMSO)<sub>2</sub>] (<strong>QY3</strong>), and [RuCl<sub>2</sub>(yc4)<sub>2</sub>(DMSO)<sub>2</sub>]·1.25H<sub>2</sub>O (<strong>QY4</strong>), 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 <strong>QY4</strong> 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 IC<sub>50</sub> value of 5.02 ± 0.14 μM and low toxicity against embryonic kidney HEK293 (e293) normal cells under equal conditions (IC<sub>50</sub> = 88.04 ± 1.03 μM). Notably, <strong>QY4</strong> exhibited higher cytotoxicity than <strong>QY1</strong>–<strong>QY3</strong>, yc1–yc4, and cisplatin. <strong>QY4</strong> and <strong>QY1</strong>, especially <strong>QY4</strong>, induced R9LC apoptosis via mitochondrial dysfunction, which involved mitochondrial membrane potential (MP) damage, ROS/Ca<sup>2+</sup> activation, and apoptosis protein up-regulation. Thus, these coumarin ruthenium(II) coordination compounds are promising mitochondria-targeting anticancer agents.</p></div>","PeriodicalId":20278,"journal":{"name":"Polyhedron","volume":"263 ","pages":"Article 117192"},"PeriodicalIF":2.4000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Four new ruthenium(II) coordination compounds bearing coumarin derivatives as anticancer agents\",\"authors\":\"Qi-Pin Qin , Xiao-Feng Zhou , Ling-Qi Du , Yue-Jiao Liang , Jin-Yuan Cai , Song Sun , Yan Yang\",\"doi\":\"10.1016/j.poly.2024.117192\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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, [RuCl<sub>2</sub>(yc1)<sub>2</sub>(DMSO)<sub>2</sub>] (<strong>QY1</strong>), [RuCl<sub>2</sub>(yc2)<sub>2</sub>(DMSO)<sub>2</sub>] (<strong>QY2</strong>), [RuCl<sub>2</sub>(yc3)<sub>2</sub>(DMSO)<sub>2</sub>] (<strong>QY3</strong>), and [RuCl<sub>2</sub>(yc4)<sub>2</sub>(DMSO)<sub>2</sub>]·1.25H<sub>2</sub>O (<strong>QY4</strong>), 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 <strong>QY4</strong> 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 IC<sub>50</sub> value of 5.02 ± 0.14 μM and low toxicity against embryonic kidney HEK293 (e293) normal cells under equal conditions (IC<sub>50</sub> = 88.04 ± 1.03 μM). Notably, <strong>QY4</strong> exhibited higher cytotoxicity than <strong>QY1</strong>–<strong>QY3</strong>, yc1–yc4, and cisplatin. <strong>QY4</strong> and <strong>QY1</strong>, especially <strong>QY4</strong>, induced R9LC apoptosis via mitochondrial dysfunction, which involved mitochondrial membrane potential (MP) damage, ROS/Ca<sup>2+</sup> activation, and apoptosis protein up-regulation. Thus, these coumarin ruthenium(II) coordination compounds are promising mitochondria-targeting anticancer agents.</p></div>\",\"PeriodicalId\":20278,\"journal\":{\"name\":\"Polyhedron\",\"volume\":\"263 \",\"pages\":\"Article 117192\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Polyhedron\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0277538724003681\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Polyhedron","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0277538724003681","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
Four new ruthenium(II) coordination compounds bearing coumarin derivatives as anticancer agents
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.
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.
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