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Open AccessAbstract

Ferrocenes as Potential Anticancer Drugs: Determination of the Mechanism of Action

1
Regional Centre for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Žlutý kopec 7, 65653 Brno, Czech Republic
2
Institute of Chemical Process Fundamentals of the Czech Academy of Sciences of the Czech Republic, v.v.i., Rozvojová 135, 165 02 Prague 6, Czech Republic
3
J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Dolejškova 2155/3, 182 23 Prague 8, Czech Republic
*
Author to whom correspondence should be addressed.
Presented at the 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery, Barcelona, Spain, 15–17 May 2019.
Proceedings 2019, 22(1), 16; https://doi.org/10.3390/proceedings2019022016
Published: 7 August 2019
(This article belongs to the Proceedings of The Molecules Medicinal Chemistry Symposium)
PDF [153 KB, uploaded 7 August 2019]

Abstract

Chemotherapy is an essential treatment that still plays a vital role in cancer treatment worldwide. The ferrocene derivatives of the general formula [Fe{(η5‑C5H4CH2(p‑C6H4)CH2(N‑het)}2] bearing modified six and five membered N-heterocycles were tested in vitro for their cytotoxic properties against ovarian cancer cell lines A2780 and SK-OV-3. These ferrocene complexes displayed cytotoxicity in low micromolar concentrations against both cell lines. To study cellular uptake of particular ferrocenes into tumor cells, we used differential pulse voltammetry and ICP-MS. We confirmed the crucial role of transferrin receptors in the process of intracellular accumulation of these ferrocenes. Interestingly, the rate of intracellular accumulation of particular ferrocenes clearly mirrored the cytotoxicity of these organometallic compounds. Deeper investigation of the mechanism by which ferrocenes kill tumor cells revealed induction of apoptosis associated with significant increase of reactive oxygen species. In conclusion, our screening identified several ferrocene derivatives exerting promising cytostatic activity in vitro. Further investigation led to the identification of the mechanism of action of these potential anticancer agents, which represents an important milestone in preclinical anticancer drug discovery programs. This work was supported by the project MEYS-NPS I-LO1413, MH CZ-DRO (MMCI, 00209805) and Czech Science Foundation project 17-05838S.
Keywords: ferrocene; ovarian cancer; cellular uptake; transferrin; reactive oxygen species ferrocene; ovarian cancer; cellular uptake; transferrin; reactive oxygen species
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hrstka, R.; Skoupilová, H.; Bartošík, M.; Sommerová, L.; Karban, J.; Pinkas, J. Ferrocenes as Potential Anticancer Drugs: Determination of the Mechanism of Action. Proceedings 2019, 22, 16.

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