{"title":"含有新型双喹喔啉配体的铂(II)和铜(II)配合物的抗增殖活性。","authors":"Hager Sadek El-Beshti, Zuhal Gercek, Hakan Kayi, Yasemin Yildizhan, Yuksel Cetin, Zelal Adigüzel, Gamze Güngör, Şeniz Özalp-Yaman","doi":"10.1093/mtomcs/mfae001","DOIUrl":null,"url":null,"abstract":"<p><p>Nowadays, cancer represents one of the major causes of death in humans worldwide, which renders the quest for new and improved antineoplastic agents to become an urgent issue in the field of biomedicine and human health. The present research focuses on the synthesis of 2,3,2',3'-tetra(pyridin-2-yl)-6,6'-biquinoxaline) and (2,3,2',3'-tetra(thiophen-2-yl)-6,6'-biquinoxaline) containing copper(II) and platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin were assessed with UV titration, thermal decomposition, viscometric, and fluorometric methods. The thermodynamical parameters and the temperature-dependent binding constant (K'b) values point out to spontaneous interactions between the complexes and CT-DNA via the van der Waals interactions and/or hydrogen bonding, except Cu(ttbq)Cl2 for which electrostatic interaction was proposed. The antitumor activity of the complexes against several human glioblastomata, lung, breast, cervix, and prostate cell lines were investigated by examining cell viability, oxidative stress, apoptosis-terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, in vitro migration and invasion, in vitro-comet DNA damage, and plasmid DNA interaction assays. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that Cu(ttbq)Cl2, Pt(ttbq)Cl2, and Pt(tpbq)Cl2 have the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. The wound healing and invasion analysis results also supported the higher anticancer activity of these two compounds.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849753/pdf/","citationCount":"0","resultStr":"{\"title\":\"Antiproliferative activity of platinum(II) and copper(II) complexes containing novel biquinoxaline ligands.\",\"authors\":\"Hager Sadek El-Beshti, Zuhal Gercek, Hakan Kayi, Yasemin Yildizhan, Yuksel Cetin, Zelal Adigüzel, Gamze Güngör, Şeniz Özalp-Yaman\",\"doi\":\"10.1093/mtomcs/mfae001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Nowadays, cancer represents one of the major causes of death in humans worldwide, which renders the quest for new and improved antineoplastic agents to become an urgent issue in the field of biomedicine and human health. The present research focuses on the synthesis of 2,3,2',3'-tetra(pyridin-2-yl)-6,6'-biquinoxaline) and (2,3,2',3'-tetra(thiophen-2-yl)-6,6'-biquinoxaline) containing copper(II) and platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin were assessed with UV titration, thermal decomposition, viscometric, and fluorometric methods. The thermodynamical parameters and the temperature-dependent binding constant (K'b) values point out to spontaneous interactions between the complexes and CT-DNA via the van der Waals interactions and/or hydrogen bonding, except Cu(ttbq)Cl2 for which electrostatic interaction was proposed. The antitumor activity of the complexes against several human glioblastomata, lung, breast, cervix, and prostate cell lines were investigated by examining cell viability, oxidative stress, apoptosis-terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, in vitro migration and invasion, in vitro-comet DNA damage, and plasmid DNA interaction assays. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that Cu(ttbq)Cl2, Pt(ttbq)Cl2, and Pt(tpbq)Cl2 have the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. The wound healing and invasion analysis results also supported the higher anticancer activity of these two compounds.</p>\",\"PeriodicalId\":89,\"journal\":{\"name\":\"Metallomics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-02-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849753/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metallomics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/mtomcs/mfae001\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metallomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/mtomcs/mfae001","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
如今,癌症已成为全球人类死亡的主要原因之一,因此,寻找新的和更好的抗肿瘤药物已成为生物医学和人类健康领域的一个紧迫问题。本研究的重点是合成 2,3,2',3'-tetra(pyridin-2-yl)-6,6'-biquinoxaline) 和 (2,3,2',3'-tetra(thiophen-2-yl)-6,6'-biquinoxaline) 含铜(II) 和铂(II) 的候选化合物作为原药。这些化合物与小牛胸腺 DNA(CT-DNA)和人血清白蛋白(HSA)的结合作用采用紫外滴定法、热分解法、粘度测定法和荧光测定法进行了评估。热力学参数和随温度变化的结合常数(K'b)值表明,除 Cu(ttbq)Cl2 外,复合物与 CT-DNA 之间通过范德华相互作用和/或氢键自发发生相互作用,而 Cu(ttbq)Cl2 则被认为具有静电作用。通过检测细胞活力(MTT)、氧化应激、细胞凋亡-TUNEL、体外迁移和侵袭、体外-Comet DNA 损伤和质粒 DNA 相互作用实验,研究了复合物对几种人类胶质母细胞瘤、肺、乳腺、宫颈和前列腺细胞系的抗肿瘤活性。U87 和 HeLa 细胞是对我们的复合物最敏感的癌细胞。复合物所产生的细胞毒性作用归因于体外活性氧的形成。研究清楚地表明,在所测试的复合物中,Cu(ttbq)Cl2、Pt(ttbq)Cl2 和 Pt(tpbq)Cl2 具有最高的 DNA 降解潜力和抗癌效果,可导致细胞凋亡。伤口愈合和侵袭分析结果也证明了这两种化合物具有更高的抗癌活性。
Antiproliferative activity of platinum(II) and copper(II) complexes containing novel biquinoxaline ligands.
Nowadays, cancer represents one of the major causes of death in humans worldwide, which renders the quest for new and improved antineoplastic agents to become an urgent issue in the field of biomedicine and human health. The present research focuses on the synthesis of 2,3,2',3'-tetra(pyridin-2-yl)-6,6'-biquinoxaline) and (2,3,2',3'-tetra(thiophen-2-yl)-6,6'-biquinoxaline) containing copper(II) and platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin were assessed with UV titration, thermal decomposition, viscometric, and fluorometric methods. The thermodynamical parameters and the temperature-dependent binding constant (K'b) values point out to spontaneous interactions between the complexes and CT-DNA via the van der Waals interactions and/or hydrogen bonding, except Cu(ttbq)Cl2 for which electrostatic interaction was proposed. The antitumor activity of the complexes against several human glioblastomata, lung, breast, cervix, and prostate cell lines were investigated by examining cell viability, oxidative stress, apoptosis-terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, in vitro migration and invasion, in vitro-comet DNA damage, and plasmid DNA interaction assays. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that Cu(ttbq)Cl2, Pt(ttbq)Cl2, and Pt(tpbq)Cl2 have the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. The wound healing and invasion analysis results also supported the higher anticancer activity of these two compounds.