Platinum-based chemotherapeutics are a cornerstone in the treatment of many malignancies. However, their dose-limiting side effects have rooted efforts to develop new drug candidates with higher selectivity for tumor tissues and less problematic side effects. Here, we developed a cytotoxic platinum(II) complex based on Zeise's salt, containing the nonsteroidal anti-inflammatory drug acetylsalicylic acid and alanine as ligands (4). The previously developed complex (5) displayed high reactivity against sulfur-containing biomolecules; therefore, we put the focus on the optimization of the structure regarding its stability. Different amino acids were used as biocompatible chelating ligands to achieve this aim. Differences in the coordination sphere caused pronounced changes in the stability of Zeise-type precursors 1-3. Coordination with l-Ala through N in the trans position to ethylene showed the most promising results and was employed to stabilize 5. As a result, complex 4 showed improved stability and cytotoxicity, outperforming both 5 and 1.

Amino Acids as Chelating Ligands for Platinum: Enhanced Stability in an Aqueous Environment Promoted by Biocompatible Molecules / Cucchiaro, Andrea; Scherfler, Amelie; Corinti, Davide; Berden, Giel; Oomens, Jos; Wurst, Klaus; Gust, Ronald; Crestoni, Maria Elisa; Kircher, Brigitte; Cziferszky, Monika. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 66:22(2023), pp. 15256-15268. [10.1021/acs.jmedchem.3c01340]

Amino Acids as Chelating Ligands for Platinum: Enhanced Stability in an Aqueous Environment Promoted by Biocompatible Molecules

Davide Corinti;Maria Elisa Crestoni;
2023

Abstract

Platinum-based chemotherapeutics are a cornerstone in the treatment of many malignancies. However, their dose-limiting side effects have rooted efforts to develop new drug candidates with higher selectivity for tumor tissues and less problematic side effects. Here, we developed a cytotoxic platinum(II) complex based on Zeise's salt, containing the nonsteroidal anti-inflammatory drug acetylsalicylic acid and alanine as ligands (4). The previously developed complex (5) displayed high reactivity against sulfur-containing biomolecules; therefore, we put the focus on the optimization of the structure regarding its stability. Different amino acids were used as biocompatible chelating ligands to achieve this aim. Differences in the coordination sphere caused pronounced changes in the stability of Zeise-type precursors 1-3. Coordination with l-Ala through N in the trans position to ethylene showed the most promising results and was employed to stabilize 5. As a result, complex 4 showed improved stability and cytotoxicity, outperforming both 5 and 1.
2023
Zeise’s salt; IRMPD spectroscopy; bioinorganic chemistry
01 Pubblicazione su rivista::01a Articolo in rivista
Amino Acids as Chelating Ligands for Platinum: Enhanced Stability in an Aqueous Environment Promoted by Biocompatible Molecules / Cucchiaro, Andrea; Scherfler, Amelie; Corinti, Davide; Berden, Giel; Oomens, Jos; Wurst, Klaus; Gust, Ronald; Crestoni, Maria Elisa; Kircher, Brigitte; Cziferszky, Monika. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 66:22(2023), pp. 15256-15268. [10.1021/acs.jmedchem.3c01340]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1693667
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