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Serbian Association for Cancer Research SDIRSACR

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In vitro antitumor activity of novel Schiff base-derived palladium complexes

Jovana S. Dragojevic , Damnjan Pantić , Petar Čanović ,Vera M. Divac , Žiko Milanović , Kristina Milisavljević , Marina
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D. Kostić 4
1Department of Chemistry, Faculty of Science, University of Kragujevac, Kragujevac, Serbia
2Department of Surgery,Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
3Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
4Department of Science,Institute for Information Technologies, University of Kragujevac,Kragujevac, Serbia
Keywords: drug design, biogenic amines, cancer of prostate, palladium, apoptosis, molecular docking simulation

Background: The treatment of cancer represents the most challenging issue of modern science, particularly due to
the resistance of tumor cells to many utilized protocols and treatments, as well as serious side effects. Thus, the
development of new anti-cancer agents with increased activity and lowered toxicity is one of the major directions
of modern science. Due to structural resemblance with well-known platinum compounds, palladium-based metallo-
drugs have found a significant place in cancer research. In this study, we aimed to determine the cytotoxic effect of
three novel synthesized Pd(II) complexes with Schiff bases as ligands, on the PC-3 and DU-145 cell lines, along with
healthy fibroblast cell line MRC-5.
Materials and methods: Cells were treated with ligands and palladium complexes and cell viability and death induction
upon treatment were examined.The molecular docking studies were performed to support experimentally obtained
results. In addition, the fluorometric quenching assay was performed to determine the binding mode between tested
complexes and the DNA molecule.
Results: All screened complexes showed high cytotoxic activity toward selected cell lines, while complex 2c combining
salicylic and tryptamine structural motifs, demonstrated even better activity than cisplatin for both tested cell lines,
with IC values of 7.1 µM (DU-145) and 8.6 µM (PC-3). Flow cytometry analysis showed that all complexes are capable of
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inducing apoptosis through the Bcl-2 and caspase family activation. Sophisticated molecular docking studies supported
the experimental findings, while fluorescence assay indicated that complexes interact with double-helical DNA through
both binding modes, the intercalation and minor groove binding.
Conclusions: The findings arising from this study have underscore the selective anticancer potential of the newly
synthesized Pd(II) complexes (2a–c), particularly their preferential activity against human prostate cancer cell lines.
Taking into consideration the fact thatphysico-chemical and pharmacological properties of Schiff bases can be easily
tuned through structural modification, these results offer numerous possibilities for further manipulation of ligand and
complex structure in order to find more effective, more selective and less toxic anti-cancer metallo-drug candidates.

Acknowledgments: The authors thank the Ministry of Science, Technological Development and Innovation of the
Republic of Serbia (Agreements No 451-03-136/2025-03/200378, 451-03-66/2024-03/200122, 451-03-65/2024-
03/200122).

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