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We thank Dr. A. & Aacute;lvarez-Valdes for their early contribution to this work. This research was funded by CTQ2015-68779-R and PID2019-106220RB-I00, granted by Agencia Estatal de Investigacion from the Spanish Ministerio de Ciencia e Innovacion and Ministerio de Economia y Competitividad. All biological studies were funded by the Austrian Research Service (FWF) project FG3 and P37111. Theresa Mendrina was funded via the Obermann-Mahlke Stiftung.

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

Publicated to:INORGANIC CHEMISTRY FRONTIERS (): - - 2025-05-12 (), DOI: 10.1039/d5qi00674k

Authors: Fabra, David; Mendrina, Theresa; Matesanz, Ana I; Medrano, Angeles; Pitek, Rastislav; Poetsch, Isabella; Berger, Walter; Heffeter, Petra; Quiroga, Adoracion G

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Abstract

The design of trans-platinum(ii) complexes marked a significant turning point in the development of unconventional anticancer metallodrugs. Compared to cisplatin, these complexes induce 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, and MCF10A) cell lines, finding that the complex with only one acetate trans to a chlorido group is more active and selective than the complex with two acetates (X = X '). Furthermore, the two complexes differ from cisplatin in their cellular uptake route as well as mode of action by inducing cancer cell death via non-DNA-associated mechanisms.

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