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Updated: Jun 12, 2025
Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Structural variations in the trans-carboxylate/chlorido axis that impact the mode of action of Pt(ii) complexes
David Fabra1, Theresa Mendrina2,3, Ana I Matesanz1
1Department of Inorganic Chemistry, School of Sciences, Universidad Autónoma de Madrid (UAM) Madrid 28049 Spain adoracion.gomez@uam.es.
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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