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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
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Palladium(II) Complexes with Noncovalent Interactions with DNA: Solution Speciation Controlled by Solvent Identity,
David Fabra1, János P Mészáros2, Ana I Matesanz1
1Department of Inorganic Chemistry, (IAdChem) Universidad Autónoma de Madrid, Calle Francisco Tomás y Valiente, 7, 28049 Madrid, Spain.
Inorganic Chemistry
|November 12, 2025
Summary
This study explores how modifying thiosemicarbazone ligands impacts their properties and interactions with palladium(II). These palladium complexes show varied antiproliferative effects against cancer and bacterial cells.
Area of Science:
- Medicinal Chemistry
- Coordination Chemistry
- Bioinorganic Chemistry
Background:
- Thiosemicarbazone ligands exhibit tunable reactivity through coordination with metal ions like palladium(II).
- Imidazole serves as a bioisostere, and modifications to thiosemicarbazones can alter their physicochemical properties.
Purpose of the Study:
- To investigate the impact of N4-substituent modification (p-chlorophenyl group) on thiosemicarbazone properties and palladium(II) complex bioactivity.
- To assess how these modifications influence hydrophilic properties, solution stability, and target interactions.
Main Methods:
- Synthesis and characterization of novel thiosemicarbazone ligands and their palladium(II) complexes.
- Evaluation of ligand and complex properties, including tautomerism, hydrophilicity, and solution integrity.
- Assessment of antiproliferative activity against various cell types.
Main Results:
- The p-chlorophenyl substitution altered the hydrophilic properties and solution stability of the thiosemicarbazone ligands.
- Coordination to palladium(II) significantly modulated the bioactivity of the ligands.
- Palladium(II) complexes exhibited differential antiproliferative effects, enhancing activity against cancer cells while reducing it against bacterial cells.
Conclusions:
- Custom design of thiosemicarbazone ligands and their palladium(II) complexes offers a strategy for modulating biological activity.
- The observed differential bioactivity highlights the potential for developing targeted therapeutic agents.
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