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Probing Cells: Evaluating Cytotoxicity

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Gold(I,III) Complexes Designed for Selective Targeting and Inhibition of Zinc Finger Proteins

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Abstract

Auranofin is an FDA approved drug for the treatment of rheumatoid arthritis. In a repurposing effort, it has been extensively tested as an anticancer drug throughout the past decade. Regardless of the potent cytotoxicity observed for auranofin, there are many reports on lack of selectivity. Inspired by the structure of auranofin, and aiming to improve the cytotoxic selectivity, we decided to evaluate the cytotoxicity of the Au(I)-phosphine series of compounds. The correlation between chemical structure and reactivity of the compounds with model biomolecules such as N-Ac-Cys and ZnFs was deeply discussed in Chaps. 1 and 3 . Furthermore, the very same aspects that govern reactivity in the molecular level, such as the basicity and bulkiness of the phosphine ligand, σ-donating properties and lability of the co-ligands L (L = Cl or 4-dimethylaminopyridine, dmap) and overall charge of the compounds (neutral vs. cationic) are also expected to play a role in cytotoxic response, establishing an interesting set of parameters that can be correlated.

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Authors and Affiliations

  1. Institute of Chemistry, University of Campinas, Campinas, Brazil

    Raphael Enoque Ferraz de Paiva

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  1. Raphael Enoque Ferraz de Paiva
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Correspondence to Raphael Enoque Ferraz de Paiva .

Appendix

Appendix

1.1 Cellular Morphology

See Fig. 4.6.

Fig. 4.6
figure 6

Morphology of CEM cell line untreated and treated with IC75-concentrations of compounds [AuCl(Et3P)] (I-1), [Au(dmap)(Et3P)]+ (I-2) and auranofin (I-3)

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1.2 Flow Cytometry

See Fig. 4.7.

Fig. 4.7
figure 7

Flow cytometry profile of CEM cell treated with IC25 concentrations for 6 h

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1.3 Mechanism of Auranofin-Induced Apoptosis

See Fig. 4.8.

Fig. 4.8
figure 8

Apoptotic mechanism caused by auranofin on CEM cells. The mechanism is consistent with previous results on HL-60 leukemia cells treated with auranofin [15]

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Ferraz de Paiva, R.E. (2018). Probing Cells: Evaluating Cytotoxicity. In: Gold(I,III) Complexes Designed for Selective Targeting and Inhibition of Zinc Finger Proteins. Springer Theses. Springer, Cham. https://doi.org/10.1007/978-3-030-00853-6_4

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