Abstract
The interaction between human serum transferrin (hTf) and three promising organometallic Ru (II)- (η5-C5H5) derived complexes, that have already shown strong in vitro cytotoxicity towards human cancer cell lines, has been investigated using fluorescence spectroscopic techniques. The results suggested that the formation of Ru-hTf systems involves a dynamic collision. The binding process occurs spontaneously (ΔG < 0), mainly driven by hydrophobic interactions. Additional docking studies show that all complexes bind preferably to a specific hydrophobic pocket in the C2-subdomain as already observed for other metal-cyclopentadienyl (MCp) complexes and are in agreement with the experimental results. With these studies we hope to contribute to the understanding of the mechanism of action of these promising cytotoxic agents, thus providing clues for a more rational design.
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Abbreviations
- 2,2′-Bipy:
-
2,2′-Bipyridine
- A2780:
-
Ovarian carcinoma cells
- Cp:
-
Cyclopentadienyl
- apohTf:
-
Human serum apo-transferrin
- HSA:
-
Human serum albumin
- hTf:
-
Human serum transferrin
- HT29:
-
Colon cancer cells
- MCF7:
-
Breast cancer cells (estrogen independent, Erα+)
- MDAMB231:
-
Breast cancer cells (estrogen independent, Erα−)
- Me2bipy:
-
4,4′-Dimethyl-2,2′-bipyridine
- mTPPMSNa:
-
Ph2P(3-OSO2C6H4)−/diphenylphosphane-benzene-3-sulfonate
- PC3:
-
Prostate cancer cells (androgen independent)
- TrP:
-
Tryptophan
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Acknowledgements
We thank the Fundação para a Ciência e Tecnologia (FCT) for the financial support (project UIDB/00100/2020 (CQE), UIDB/04046/2020 and UIDP/04046/2020 (BioISI), and also Programa Operacional Regional de Lisboa (Lisboa 2020), Portugal 2020, FEDER/FN, and the European Union under project number 28455 (LISBOA-01-0145-FEDER-028455, PTDC/QUI-QFI/28455/2017). T.S. Morais thanks FCT for CEECIND 2017 Initiative for the project CEECIND/00630/2017 (acknowledging FCT, POPH and FSE- European Social Fund). P.J. Costa thank FCT for the Investigador FCT Program IF/00069/2014 and exploratory project IF/00069/2014/CP1216/CT0006. F.C. Santos thanks FCT for her Doctoral Grant (SFRH/BD/108031/2015).
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Santos, F.C., Costa, P.J., Garcia, M.H. et al. Binding of RuCp complexes with human apo-transferrin: fluorescence spectroscopy and molecular docking methods. Biometals 34, 1029–1042 (2021). https://doi.org/10.1007/s10534-021-00325-w
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DOI: https://doi.org/10.1007/s10534-021-00325-w