Page 87 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

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Ruthenium (II) complexes as promising candidates for cancer therapy

1
Andreja Leskovac , Sandra Petrovic 1
1 Vinca Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, M. Petrovica
-Alasa 12-14, 11001 Belgrade, Serbia

Background: Acting as single compounds, both Ru(II) complexes and phenothiazines are considered
promising anticancer drugs with inhibitory effects on cancer cell growth and differentiation. The complexes
synthesized by a combination of Ru(II) with N-alkylphenothiazines (chlorpromazine hydrochloride (1),
thioridazine hydrochloride (2) and trifluoperazine (3)) are reported to reduce the cell viability of some
cancer cell lines. This study explored whether the selected complexes affect the redox homeostasis and
genome integrity of normal human blood cells and induce inhibition of membrane-bound enzymes at
pharmacologically relevant doses. Material and Methods: To evaluate the genotoxic potential of
complexes, the incidences of micronuclei and cell proliferation index were investigated in cultured human
peripheral blood lymphocytes. The redox modulating effects were examined by measuring the catalase
activity and malondialdehyde level as a measure of oxidative stress. The influence of complexes on enzymes
+
+
Na /K -ATPase and AChE bound to the cell membrane was also analyzed. Results: The selected complexes
did not affect the activity of Na+/K+-ATPase, while AChE activity was inhibited in a dose-dependent manner.
Furthermore, the results have shown that complexes 1 and 2 displayed cytotoxic and prooxidant action.
Conversely, complex 3 disturbed the viability and redox homeostasis of the normal cells only at the highest
concentration applied. Conclusion: According to our data, all investigated complexes have the potential for
use in anticancer therapy. Complex 3 has shown the most promising effects and should be further examined
as part of the novel therapeutic strategy to develop a more effective and less toxic therapeutic agent.
Keywords: Ruthenium (II), N-alkyl phenothiazine, cytotoxicity, redox homeostasis, anticancer agents

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