Structural variations in the <i>trans</i>-carboxylate/chlorido axis that impact the mode of action of Pt(ii) complexes
- Author(s)
- David Fabra, Theresa Mendrina, Ana I Matesanz, Ángeles Medrano, Rastislav Pitek, Isabella Poetsch, Walter Berger, Petra Heffeter, Adoración G Quiroga
- 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.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Universidad Autónoma de Madrid, Medizinische Universität Wien
- Journal
- Inorganic Chemistry Frontiers
- ISSN
- 2052-1553
- DOI
- https://doi.org/10.1039/d5qi00674k
- Publication date
- 05-2025
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301904 Cancer research
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/07e01dfe-0290-4560-ae40-61d0940fd5ba