1- and 1,5-Aminoalkylamine substituted anthraquinones (AAQs, 1C3 and 1,5C3) were peptide coupled to 1-, 2-, and 3-pyrrole lexitropsins to generate compounds that incorporated both DNA minor groove and intercalating moieties. The corresponding platinum(II) amidine complexes were synthesized through a synthetically facile amine-to-platinum mediated nitrile ‘Click’ reaction. The precursors as well as the corresponding platinum(II) complexes were biologically evaluated in 2D monolayer cells and 3D tumour cell models. Despite having cellular accumulation levels that were up to five-fold lower than that of cisplatin, the platinum complexes had cytotoxicities that were only three-fold lower. Accumulation was lowest for the complexes with two or three pyrrole groups, but the latter was the most active of the complexes exceeding the activity of cisplatin in the MDA-MB-231 cell line. All compounds showed moderate to good penetration into spheroids of DLD-1 cells with the distributions being consistent with active uptake of the pyrrole containing complexes in regions of the spheroids starved of nutrients.

Graphic abstract

中文翻译：

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新型聚酰胺脒蒽醌铂 (II) 复合物：2D 和 3D 细胞培养模型中的细胞毒性、细胞积累和荧光分布

1-和 1,5-氨基烷基胺取代的蒽醌（AAQ、1C3 和 1,5C3）是肽偶联到 1-、2- 和 3-吡咯 lexitropsins 以生成结合 DNA 小沟和嵌入部分的化合物。相应的铂 (II) 脒配合物是通过合成简便的胺对铂介导的腈“点击”反应合成的。在 2D 单层细胞和 3D 肿瘤细胞模型中对前体以及相应的铂 (II) 配合物进行了生物学评估。尽管细胞积累水平比顺铂低五倍，但铂配合物的细胞毒性仅低三倍。具有两个或三个吡咯基团的配合物的积累最低，但后者是活性最高的复合物，超过了 MDA-MB-231 细胞系中顺铂的活性。所有化合物均显示出中等至良好的 DLD-1 细胞球体渗透率，其分布与缺乏营养的球体区域中含有吡咯的复合物的主动吸收一致。

图形摘要