Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. General Information
4.2. Chemistry
4.2.1. General Procedure for the Synthesis of 3-Benzyloxy-d-secoalcohols 1, 6
4.2.2. General Procedure for the Synthesis of 3-Hydroxy-d-secoestrones 7, 8
4.2.3. General Procedure for the Synthesis of 3-(Prop-2-inyloxy)-d-secoestrones 9, 10
4.2.4. General Procedure for the “Click” Reaction
4.3. Determination of Antiproliferative Activities
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Comp. | Conc. (µM) | Inhibition (%) ± SEM (Calculated IC50) 1 | |||||||
---|---|---|---|---|---|---|---|---|---|
A2780 | Hela | SiHa | C33A | MCF-7 | T47D | MDA-MB-231 | MDA-MB-361 | ||
1 | 10 | 42.3 ± 0.9 | 31.4 ± 1.6 | - 2 | 39.2 ± 0.6 | 81.3 ± 0.7 | 26.1 ± 2.0 | - | 28.2 ± 0.4 |
30 | 97.5 ± 0.1 | 97.9 ± 0.3 | 84.3 ± 0.9 | 86.9 ± 0.7 | 97.4 ± 0.3 | 87.2 ± 0.9 | 84.5 ± 0.9 | 87.6 ± 0.4 | |
(6.4) | |||||||||
6 | 10 | 43.6 ± 2.4 | 20.1 ± 1.8 | - | 40.4 ± 2.1 | - | - | - | - |
30 | 55.4 ± 2.5 | 60.3 ± 1.4 | 49.7 ± 1.4 | 53.8 ± 1.1 | 36.4 ± 1.2 | 59.6 ± 0.8 | 49.3 ± 1.6 | 77.2 ± 1.3 | |
7 | 10 | - | - | - | 40.5 ± 0.8 | 24.3 ± 2.6 | - | - | - |
30 | 35.1 ± 0.8 | 40.7 ± 1.7 | - | 42.3 ± 1.8 | 51.6 ± 2.9 | - | - | - | |
8 | 10 | - | 23.7 ± 0.9 | - | - | - | - | - | - |
30 | - | 64.5 ± 1.1 | - | - | - | 23.0 ± 1.7 | - | - | |
9 | 10 | 22.4 ± 1.0 | 21.5 ± 0.8 | - | 30.0 ± 1.1 | - | - | 36.8 ± 2.7 | - |
30 | 70.7 ± 0.4 | 89.3 ± 1.9 | 84.5 ± 0.5 | 70.1 ± 0.7 | 52.5 ± 1.0 | 37.7 ± 1.3 | 81.0 ± 1.1 | 59.0 ± 2.9 | |
10 | 10 | - | - | - | - | - | - | - | - |
30 | 29.7 ± 1.9 | 36.9 ± 1.8 | - | 39.9 ± 1.1 | 23.3 ± 0.6 | 45.5 ± 0.6 | 28.2 ± 2.2 | - | |
12a | 10 | 81.5 ± 1.1 | 85.4 ± 0.3 | 21.2 ± 1.1 | 90.0 ± 0.3 | 66.3 ± 0.3 | 51.0 ± 1.1 | 53.5 ± 1.2 | 59.3 ± 1.4 |
30 | 88.0 ± 0.1 | 91.7 ± 0.3 | 34.5 ± 1.2 | 95.1 ± 0.2 | 74.5 ± 1.7 | 54.4 ± 1.8 | 59.6 ± 1.8 | 45.2 ± 1.1 | |
(0.9) | (1.1) [23] | (1.8) [23] | (1.5) | ||||||
12b | 10 | 96.8 ± 0.2 | 52.6 ± 0.9 | 48.1 ± 0.8 | 86.8 ± 0.8 | 71.6 ± 1.0 | 65.7 ± 1.4 | 58.3 ± 0.7 | 87.2 ± 0.5 |
30 | 97.4 ± 0.1 | 65.4 ± 0.9 | 64.3 ± 1.0 | 93.9 ± 0.9 | 73.9 ± 1.0 | 66.4 ± 1.2 | 86.1 ± 0.3 | 89.3 ± 1.1 | |
(3.8) | (5.0) | (5.0) | (8.3) | (4.4) | |||||
12c | 10 | 83.3 ± 0.5 | 27.1 ± 1.7 | - | 57.5 ± 1.8 | - | - | 33.6 ± 0.8 | 47.1 ± 2.9 |
30 | 93.4 ± 0.1 | 66.0 ± 2.4 | 35.6 ± 0.3 | 84.6 ± 0.9 | 66.1 ± 1.7 | 53.0 ± 1.6 | 48.9 ± 0.7 | 45.6 ± 0.6 | |
(5.4) | (8.3) | ||||||||
12d | 10 | 20.5 ± 1.2 | 30.9 ± 3.0 | - | 25.3 ± 1.5 | - | - | - | - |
30 | 29.0 ± 2.0 | 45.9 ± 1.1 | - | 64.0 ± 1.8 | 29.5 ± 2.7 | 28.9 ± 0.9 | - | 45.5 ± 1.2 | |
12e | 10 | 86.4 ± 0.3 | 46.3 ± 2.5 | 25.5 ± 2.0 | 81.4 ± 1.9 | 61.1 ± 1.6 | 41.5 ± 2.0 | 49.8 ± 0.7 | 47.5 ± 0.7 |
30 | 89.6 ± 0.3 | 72.5 ± 1.1 | 23.2 ± 1.2 | 88.9 ± 0.6 | 63.4 ± 0.9 | 49.7 ± 2.5 | 48.8 ± 0.9 | 46.7 ± 1.0 | |
(4.6) | (5.4) | (6.6) | |||||||
13a | 10 | 73.4 ± 0.9 | 70.0 ± 0.7 | 41.8 ± 1.7 | 80.0 ± 0.5 | 39.4 ± 1.2 | 36.6 ± 0.7 | 38.2 ± 2.2 | 65.8 ± 1.0 |
30 | 83.8 ± 0.8 | 90.9 ± 0.3 | 37.1 ± 1.0 | 93.9 ± 0.1 | 73.8 ± 1.1 | 69.1 ± 0.6 | 59.7 ± 1.6 | 48.6 ± 1.4 | |
(3.0) | (5.3) | (4.4) | |||||||
13b | 10 | 54.3 ± 0.8 | 33.9 ± 1.1 | - | 26.6 ± 1.8 | - | 43.2 ± 0.3 | 36.7 ± 1.8 | - |
30 | 81.0 ± 0.1 | 74.4 ± 0.9 | 49.4 ± 0.8 | 86.1 ± 0.6 | 65.6 ± 1.9 | 89.3 ± 0.8 | 56.8 ± 1.2 | 48.7 ± 1.0 | |
(9.8) | |||||||||
13c | 10 | - | 21.3 ± 2.3 | - | - | - | - | - | - |
30 | 52.7 ± 1.9 | 40.6 ± 0.9 | - | 41.7 ± 1.2 | 20.1 ± 0.8 | 39.4 ± 1.7 | 28.1 ± 0.7 | 25.7 ± 2.8 | |
13d | 10 | 20.0 ± 1.9 | 24.4 ± 1.3 | - | 26.1 ± 0.9 | - | - | - | - |
30 | 44.8 ± 1.1 | 36.9 ± 0.8 | 23.0 ± 1.2 | 66.3 ± 0.6 | 30.8 ± 1.7 | 44.4 ± 1.7 | 37.5 ± 1.6 | 40.3 ± 2.1 | |
13e | 10 | - | - | - | - | - | - | - | - |
30 | 29.1 ± 2.3 | 48.3 ± 2.0 | - | 34.2 ± 1.3 | - | 22.8 ± 1.9 | - | - | |
Cisplatin | 10 | 83.6 ± 1.2 | 42.6 ± 2.3 | 88.6 ± 0.5 | 83.8 ± 0.8 | 66.9 ± 1.8 | 51.0 ± 2.0 | - | 67.5 ± 1.0 |
30 | 95.0 ± 0.3 | 99.9 ± 0.3 | 90.2 ± 1.8 | 94.0 ± 0.6 | 96.8 ± 0.4 | 57.9 ± 1.5 | 71.5 ± 1.2 | 87.8 ± 1.1 | |
(1.3) | (12.4) | (7.8) | (3.7) | (5.8) | (9.8) | (19.1) | (3.7) |
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Szabó, J.; Jerkovics, N.; Schneider, G.; Wölfling, J.; Bózsity, N.; Minorics, R.; Zupkó, I.; Mernyák, E. Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative. Molecules 2016, 21, 611. https://doi.org/10.3390/molecules21050611
Szabó J, Jerkovics N, Schneider G, Wölfling J, Bózsity N, Minorics R, Zupkó I, Mernyák E. Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative. Molecules. 2016; 21(5):611. https://doi.org/10.3390/molecules21050611
Chicago/Turabian StyleSzabó, Johanna, Nóra Jerkovics, Gyula Schneider, János Wölfling, Noémi Bózsity, Renáta Minorics, István Zupkó, and Erzsébet Mernyák. 2016. "Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative" Molecules 21, no. 5: 611. https://doi.org/10.3390/molecules21050611
APA StyleSzabó, J., Jerkovics, N., Schneider, G., Wölfling, J., Bózsity, N., Minorics, R., Zupkó, I., & Mernyák, E. (2016). Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative. Molecules, 21(5), 611. https://doi.org/10.3390/molecules21050611