Kinetically inert platinum(IV) complexes are a chemical strategy to overcome the impediments of standard platinum(II) antineoplastic drugs like cisplatin, oxaliplatin and carboplatin. In this study, we reported the syntheses and structural characterisation of three platinum(IV) complexes that incorporate 5-benzyloxyindole-3-acetic acid, a bioactive ligand that integrates an indole pharmacophore. The purity and chemical structures of the resultant complexes, P-5B3A, 5-5B3A and 56-5B3A were confirmed via spectroscopic means. The complexes were evaluated for anticancer activity against multiple human cell lines. All complexes proved to be considerably more active than cisplatin, oxaliplatin and carboplatin in most cell lines tested. Remarkably, 56-5B3A demonstrated the greatest anticancer activity, displaying GI50 values between 1.2 and 150 nM. Enhanced production of reactive oxygen species paired with the decline in mitochondrial activity as well as inhibition of histone deacetylase were also demonstrated by the complexes in HT29 colon cells.

中文翻译：

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在轴向位置结合吲哚基衍生物 5-苄氧基吲哚-3-乙酸的铂 (IV) 前药表现出显着的抗癌活性

动力学惰性铂 (IV) 配合物是一种化学策略，可克服标准铂 (II) 抗肿瘤药物（如顺铂、奥沙利铂和卡铂）的障碍。在这项研究中，我们报道了三种铂 (IV) 配合物的合成和结构表征，其中包含 5-苄氧基吲哚-3-乙酸，一种整合吲哚药效团的生物活性配体。通过光谱手段确认了所得复合物P-5B3A、5-5B3A和56-5B3A的纯度和化学结构。评估了复合物针对多种人类细胞系的抗癌活性。在大多数测试的细胞系中，所有复合物均被证明比顺铂、奥沙利铂和卡铂活性更高。值得注意的是，56-5B3A 表现出最强的抗癌活性，GI50 值在 1.2 至 150 nM 之间。 HT29 结肠细胞中的复合物还证明了活性氧产生的增加与线粒体活性的下降以及组蛋白脱乙酰酶的抑制相结合。