Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity
Abstract
:1. Introduction
2. Results
2.1. Synthesis of the Heterodimers (11–14)
2.2. Pharmacology
2.3. Computational Simulations
3. Discussion
4. Methods and Materials
4.1. Chemistry
General Procedure for the Synthesis of Heterodimers (11–14)
4.2. Pharmacology
4.2.1. Antiproliferative (MTT) Assay
4.2.2. Cell Cycle Analysis by Flow Cytometry
4.2.3. Hoechst 33258—Propidium Iodide (HOPI) Double Staining
4.2.4. Tubulin Polymerization Assay
4.3. Computational Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Conc. | Inhibition, % ± SEM | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
11 | 12 | 13 | 14 | Cisplatin | |||||||||
Cell Lines | µM | Mean | SEM | Mean | SEM | IC50 (µM) | Mean | SEM | Mean | SEM | Mean | SEM | IC50 (µM) |
HeLa | 10 | 3.06 | 0.33 | 94.20 | 0.18 | 1.71 | 11.20 | 2.67 | 43.33 | 2.93 | 42.60 | 2.30 | 12.40 |
30 | 4.17 | 1.39 | 96.98 | 0.16 | 11.97 | 0.94 | 48.03 | 1.65 | 99.90 | 0.30 | |||
SiHa | 10 | 4.97 | 1.99 | 86.91 | 0.78 | 0.97 | 9.82 | 3.08 | 45.61 | 2.12 | 88.60 | 0.50 | 7.80 |
30 | 16.42 | 2.14 | 93.43 | 0.72 | 28.67 | 0.85 | 75.29 | 1.92 | 90.20 | 1.80 | |||
C33A | 10 | 39.84 | 2.78 | 69.99 | 1.57 | 2.99 | 28.03 | 1.16 | 52.76 | 1.13 | 83.80 | 0.80 | 3.70 |
30 | 43.27 | 2.32 | 96.46 | 0.21 | 41.84 | 1.28 | 54.21 | 2.20 | 94.00 | 0.60 | |||
A2780 | 10 | 24.40 | 1.00 | 78.21 | 2.96 | 3.44 | 27.32 | 2.02 | 33.44 | 1.11 | 83.60 | 1.20 | 1.30 |
30 | 28.35 | 1.49 | 92.65 | 1.05 | 35.35 | 3.03 | 27.09 | 0.81 | 95.00 | 0.30 | |||
MCF-7 | 10 | 7.93 | 3.54 | 88.68 | 1.24 | 1.80 | 1.40 | 3.69 | 55.78 | 2.57 | 66.90 | 1.80 | 5.80 |
30 | 6.12 | 3.05 | 89.95 | 0.93 | 46.56 | 4.02 | 58.14 | 1.89 | 96.80 | 0.40 | |||
T-47D | 10 | 10.90 | 2.81 | 75.42 | 0.52 | 1.04 | 17.57 | 1.99 | 58.85 | 2.55 | 51.00 | 2.00 | 9.80 |
30 | 11.46 | 0.90 | 87.13 | 1.53 | 53.64 | 2.59 | 58.76 | 2.15 | 57.90 | 1.50 | |||
MDA-MB-231 | 10 | 19.34 | 1.42 | 90.00 | 0.95 | 2.04 | 32.05 | 3.92 | 24.45 | 2.44 | 20.84 | 0.81 | 19.10 |
30 | 23.65 | 2.16 | 93.40 | 1.06 | 38.37 | 2.58 | 27.98 | 2.86 | 74.47 | 1.20 | |||
MDA-MB-361 | 10 | 5.67 | 1.26 | 82.42 | 3.01 | 2.07 | 0.45 | 5.85 | 60.32 | 4.62 | 67.50 | 1.00 | 3.70 |
30 | 5.27 | 3.51 | 83.99 | 1.04 | 40.25 | 5.37 | 66.86 | 3.65 | 87.80 | 1.10 | |||
MRC-5 | 10 | n.d. | n.d. | 85.19 | 1.23 | 1.24 | n.d. | n.d. | n.d. | n.d. | 72.30 | 2.30 | 4.51 |
30 | n.d. | n.d. | 89.55 | 0.53 | n.d. | n.d. | n.d. | n.d. | 70.70 | 1.30 | |||
NIH/3T3 | 10 | n.d. | n.d. | 41.39 | 2.76 | 15.02 | n.d. | n.d. | n.d. | n.d. | 76.74 | 1.26 | 1.26 |
30 | n.d. | n.d. | 68.64 | 3.74 | n.d. | n.d. | n.d. | n.d. | 96.90 | 0.25 |
Tumor Selectivity Index | ||||
---|---|---|---|---|
NIH/3T3 | MRC-5 | |||
Cell Lines | comp 12 | cispl | comp 12 | cispl |
HeLa | 8.78 | 0.38 | 0.73 | 0.36 |
SiHa | 15.55 | 0.61 | 1.28 | 0.58 |
C33A | 5.02 | 1.28 | 0.41 | 1.22 |
A2780 | 4.37 | 3.64 | 0.36 | 3.47 |
MCF-7 | 8.35 | 0.82 | 0.69 | 0.78 |
T-47D | 14.47 | 0.48 | 1.20 | 0.46 |
MDA-MB-231 | 7.38 | 0.25 | 0.61 | 0.24 |
MDA-MB-361 | 7.26 | 1.28 | 0.60 | 1.22 |
MRC-5 | -- | -- | 1.00 | 1.00 |
NIH/3T3 | 1.00 | 1.00 | -- | -- |
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Bózsity, N.; Nagy, V.; Szabó, J.; Pálházi, B.; Kele, Z.; Resch, V.; Paragi, G.; Zupkó, I.; Minorics, R.; Mernyák, E. Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity. Int. J. Mol. Sci. 2024, 25, 4274. https://doi.org/10.3390/ijms25084274
Bózsity N, Nagy V, Szabó J, Pálházi B, Kele Z, Resch V, Paragi G, Zupkó I, Minorics R, Mernyák E. Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity. International Journal of Molecular Sciences. 2024; 25(8):4274. https://doi.org/10.3390/ijms25084274
Chicago/Turabian StyleBózsity, Noémi, Viktória Nagy, Johanna Szabó, Balázs Pálházi, Zoltán Kele, Vivien Resch, Gábor Paragi, István Zupkó, Renáta Minorics, and Erzsébet Mernyák. 2024. "Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity" International Journal of Molecular Sciences 25, no. 8: 4274. https://doi.org/10.3390/ijms25084274