Structural variations in the trans-carboxylate/chlorido axis that impact on the mode of action of Pt(II) complexes

IF 6.1 1区化学 Q1 CHEMISTRY, INORGANIC & NUCLEAR

Inorganic Chemistry Frontiers Pub Date : 2025-05-12 DOI:10.1039/d5qi00674k

David Fabra Escribano, Theresa Mendrina, Ana Isabel Matesanz, Angeles Medrano, Rastislav Pitek, Walter Berger, Isabella Poetsch, Petra Heffeter, Adoracion Gomez Quiroga

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Abstract

The design of trans-platinum(II) complexes marked a significant turning point in the design of unconventional anticancer metallodrugs. Compared to cisplatin, these complexes exhibit distinctly different cellular responses and are often active against cisplatin-resistant cell lines. In this study, we synthesized and fully characterized two new Pt(II) complexes introducing one acetate (-OCOCH3) ligand (X) into the trans-PtXX’ axis where X’ is either acetate or chlorido. We evaluated their cytotoxicity across a panel of malignant (Capan-1, B16, MCF7, HCT-116, CT26 and P31) and non-malignant (HaCaT, HUVEC, BEC, MCF10A) cell lines, finding that the complex with only one acetate in trans to a chlorido group is more active and selective than the complex with two acetates (X=X’). Furthermore, the two complexes differ in their cellular uptake route as well as mode of action from cisplatin by inducing cancer cell death via non-DNA-associated mechanisms.

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影响Pt（II）配合物作用方式的反式羧酸/氯基轴结构变化

反式铂（II）配合物的设计标志着非常规抗癌金属药物设计的一个重要转折点。与顺铂相比，这些复合物表现出明显不同的细胞反应，并且通常对顺铂耐药细胞系有活性。在这项研究中，我们合成并充分表征了两个新的Pt（II）配合物，将一个醋酸盐（-OCOCH3）配体(X)引入trans-PtXX ‘轴，其中X ’是醋酸盐或氯基。我们在一组恶性（Capan-1, B16, MCF7, HCT-116， CT26和P31）和非恶性（HaCaT， HUVEC， BEC, MCF10A）细胞系中评估了它们的细胞毒性，发现仅含有一个醋酸酯的复合物比含有两个醋酸酯的复合物（X=X '）更具活性和选择性。此外，这两种复合物通过非dna相关机制诱导癌细胞死亡，在细胞摄取途径和顺铂的作用方式上存在差异。

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