JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2021-04-10 , DOI: 10.1007/s00775-021-01862-y Ingrid O Travassos 1 , Francyelli Mello-Andrade 1, 2 , Raíssa P Caldeira 1 , Wanessa C Pires 1 , Paula F F da Silva 1 , Rodrigo S Correa 3 , Tamara Teixeira 3 , Alisson Martins-Oliveira 4 , Alzir A Batista 5 , Elisângela P de Silveira-Lacerda 1
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Abstract
Metal complexes based on ruthenium have established excellent activity with less toxicity and great selectivity for tumor cells. This study aims to assess the anticancer potential of ruthenium(II)/allopurinol complexes called [RuCl2(allo)2(PPh3)2] (1) and [RuCl2(allo)2(dppb)] (2), where allo means allopurinol, PPh3 is triphenylphosphine and dppb, 1,4-bis(diphenylphosphino)butane. The complexes were synthesized and characterized by elemental analysis, IR, UV–Vis and NMR spectroscopies, cyclic voltammetry, molar conductance measurements, as well as the X-ray crystallographic analysis of complex 2. The antitumor effects of compounds were determined by cytotoxic activity and cellular and molecular responses to cell death mechanisms. Complex 2 showed good antitumor profile prospects because in addition to its cytotoxicity, it causes cell cycle arrest, induction of DNA damage, morphological and biochemical alterations in the cells. Moreover, complex 2 induces cell death by p53-mediated apoptosis, caspase activation, increased Beclin-1 levels and decreased ROS levels. Therefore, complex 2 can be considered a suitable compound in antitumor treatment due to its cytotoxic mechanism.
Graphic abstract
中文翻译：
钌（II）/别嘌呤醇复合物通过多个靶点抑制乳腺癌进展
摘要
以钌为基础的金属配合物具有优异的活性，对肿瘤细胞的毒性小，选择性好。本研究旨在评估名为 [RuCl 2 (allo) 2 (PPh 3 ) 2 ] ( 1 ) 和 [RuCl 2 (allo) 2 (dppb)] ( 2 )的钌 (II)/别嘌呤醇复合物的抗癌潜力，其中allo是指别嘌呤醇，PPh 3是三苯基膦和dppb，1,4-双(二苯基膦基)丁烷。通过元素分析、IR、UV-Vis 和 NMR 光谱、循环伏安法、摩尔电导测量以及配合物的 X 射线晶体学分析合成并表征了配合物。2 . 化合物的抗肿瘤作用由细胞毒活性和细胞和分子对细胞死亡机制的反应决定。复合物2显示出良好的抗肿瘤前景，因为除了其细胞毒性外，它还导致细胞周期停滞、诱导 DNA 损伤、细胞形态和生化改变。此外，复合物2通过 p53 介导的细胞凋亡、半胱天冬酶激活、增加 Beclin-1 水平和降低 ROS 水平诱导细胞死亡。因此，由于其细胞毒性机制，复合物2可以被认为是抗肿瘤治疗中合适的化合物。
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