Enhanced Anticancer Potential of Pd(II)-Thiosemicarbazone Complexes: Selectivity, Mechanisms, and 3D Models
<b>Background/Objectives:</b> Cancer remains a major global health challenge, driving the search for novel chemotherapeutic agents. This study aimed to evaluate the structural and biological properties of a series of <b>Pd(II)</b> complexes containing triphenylphosphine and t...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/7/829 |
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| Summary: | <b>Background/Objectives:</b> Cancer remains a major global health challenge, driving the search for novel chemotherapeutic agents. This study aimed to evaluate the structural and biological properties of a series of <b>Pd(II)</b> complexes containing triphenylphosphine and thiosemicarbazone ligands, in order to assess their potential as anticancer agents. <b>Methods:</b> Six <b>Pd(II)</b> complexes with the general formula <b>[PdCl(PPh<sub>3</sub>)(TSC)]</b> were synthesized and fully characterized by NMR (<sup>1</sup>H, <sup>1</sup>³C, ³<sup>1</sup>P), FTIR, mass spectrometry, and X-ray diffraction. Their cytotoxic effects were investigated through in vitro assays using 2D and 3D cancer cell models, including clonogenic, wound healing, cell cycle, and apoptosis assays via flow cytometry. <b>Results:</b> Complexes from the <b>B</b> family demonstrated significantly higher cytotoxicity than those from the C family, particularly against ovarian (<i>IC</i><sub>50</sub> < 1 µM) and breast (<i>IC</i><sub>50</sub>~2 µM) cancer cell lines. These compounds exhibited superior potency and selectivity compared to cisplatin, with high selectivity indices toward non-tumor cells. Mechanistic studies revealed both cytotoxic and cytostatic effects depending on structural variations, with apoptosis identified as the primary mechanism of cell death. <b>PdB1</b>, in particular, induced a marked increase in late apoptotic populations and maintained its cytotoxic activity in 3D spheroid models by promoting disintegration, loss of cell adhesion, and nuclear fragmentation. <b>Conclusions:</b> The findings underscore the therapeutic promise of <b>Pd(II)</b> complexes, especially <b>PdB1</b>, as potent and selective antineoplastic agents capable of acting effectively in complex tumor environments and potentially overcoming chemoresistance. |
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| ISSN: | 1999-4923 |