Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells
Abstract
1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Studies
- -
- The following significant conclusions can be drawn from the analysis of the obtained data:
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- The cytotoxic effect on the studied tumor lines increases in the series: Jurkat < K562 < U937 ≤ HL-60.
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- A well-defined tendency of increasing toxicity of macrocycles with an increasing number of methylene links in dioic acid 5, at a fixed number of carbon atoms in diol 4, in each example for 4a–4d is evident; the mentioned pattern is also observed for both the conditionally normal cell line Hek293 and the normal fibroblasts.
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- The maximum cytotoxic effect on the Jurkat and K562 tumor lines was observed for compound 9d (CC50 = 11.04 and 12.11), while for the U937 cell line, compounds 9d and 8d exhibited approximately equal maximum toxicity (CC50 = 12.21 and 12.23). For the HL60 cells, the maximum effect was observed for macrocycles 9c and 9d (CC50 = 12.83 and 13.46).
3. Materials and Methods
3.1. Chemistry
3.2. Synthetic Procedures
3.2.1. The General Procedure for the Synthesis of α,ω-Alka-nZ,(n+4)Z-Dienedioic Acid 5a–d
3.2.2. The General Procedure for the Synthesis of Tetraene Macrodiolides 6a–9d
3.3. Biological Studies
3.3.1. Cell Culturing
3.3.2. Preparation of Effluent and Test Compound Solutions for Biological Testing
3.3.3. Cytotoxicity Assay
3.3.4. Mitodamage Assay
3.3.5. Cytochrome C Assay
3.3.6. Statistics
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Macrodiolide | Jurkat (CC50, nM) | SI * | K562 (CC50, nM) | SI | U937 (CC50, nM) | SI | HL60 (CC50, nM) | SI | Hek293 (CC50, nM) | SI | Fibrobl. (CC50, nM) |
---|---|---|---|---|---|---|---|---|---|---|---|
6a | 28.34 ± 2.65 | 2.6 | 24.82 ± 2.37 | 3.0 | 23.06 ± 2.11 | 3.3 | 19.76 ± 1.81 | 3.8 | 52.34 ± 5.17 | 1.4 | 76.24 ± 7.62 |
6b | 21.18 ± 1.97 | 2.9 | 21.46 ± 2.01 | 2.8 | 22.39 ± 2.24 | 2.7 | 20.37 ± 2.10 | 3.0 | 46.23 ± 3.75 | 1.3 | 61.85 ± 6.27 |
6c | 22.07 ± 2.14 | 2.6 | 19.67 ± 1.63 | 2.9 | 19.22 ± 1.87 | 3.0 | 20.09 ± 1.95 | 2.9 | 42.76 ± 4.39 | 1.3 | 58.93 ± 5.81 |
6d | 18.54 ± 1.78 | 3.2 | 16.94 ± 1.88 | 3.5 | 15.17 ± 1.56 | 3.9 | 15.67 ± 1.43 | 3.7 | 44.33 ± 4.21 | 1.3 | 59.37 ± 5.46 |
7a | 26.41 ± 2.46 | 2.5 | 23.59 ± 2.14 | 2.8 | 22.19 ± 2.34 | 3.0 | 20.38 ± 2.07 | 3.2 | 49.87 ± 4.83 | 1.3 | 67.22 ± 6.39 |
7b | 20.26 ± 2.04 | 3.0 | 18.06 ± 1.83 | 3.4 | 17.44 ± 1.71 | 3.5 | 18.24 ± 1.76 | 3.4 | 53.12 ± 4.96 | 1.1 | 62.58 ± 5.94 |
7c | 18.35 ± 1.86 | 3.2 | 16.74 ± 1.59 | 3.5 | 17.31 ± 1.62 | 3.4 | 15.32 ± 1.48 | 3.8 | 46.34 ± 3.99 | 1.2 | 59.46 ± 5.37 |
7d | 18.11 ± 1.91 | 3.3 | 17.13 ± 1.84 | 3.5 | 15.06 ± 1.43 | 3.9 | 14.46 ± 1.57 | 4.1 | 48.65 ± 4.82 | 1.2 | 60.18 ± 5.21 |
8a | 25.27 ± 2.63 | 3.4 | 22.32 ± 2.16 | 3.8 | 23.42 ± 2.27 | 3.6 | 21.84 ± 1.96 | 3.9 | 64.29 ± 5.37 | 1.3 | 86.42 ± 7.11 |
8b | 20.99 ± 2.34 | 3.2 | 19.16 ± 1.79 | 3.5 | 17.89 ± 1.83 | 3.7 | 18.73 ± 1.71 | 3.5 | 48.18 ± 4.34 | 1.3 | 67.23 ± 6.24 |
8c | 17.75 ± 1.73 | 3.6 | 16.86 ± 1.62 | 3.8 | 15.46 ± 1.49 | 4.1 | 14.68 ± 1.42 | 4.4 | 47.33 ± 4.22 | 1.3 | 64.82 ± 6.35 |
8d | 16.06 ± 1.58 | 3.9 | 15.21 ± 1.46 | 4.1 | 12.21 ± 1.37 | 5.2 | 11.06 ± 1.39 | 5.7 | 51.14 ± 5.60 | 1.2 | 63.69 ± 6.07 |
9a | 24.16 ± 2.39 | 3.3 | 20.43 ± 1.89 | 3.9 | 19.76 ± 1.97 | 4.0 | 20.22 ± 2.17 | 3.9 | 54.91 ± 5.37 | 1.4 | 79.91 ± 6.90 |
9b | 18.26 ± 2.04 | 3.3 | 17.27 ± 1.64 | 3.5 | 15.66 ± 1.53 | 3.9 | 15.64 ± 1.49 | 3.9 | 52.02 ± 5.43 | 1.1 | 61.56 ± 5.92 |
9c | 17.34 ± 1.59 | 3.4 | 14.66 ± 1.49 | 4.0 | 13.06 ± 1.31 | 4.5 | 12.83 ± 1.37 | 4.6 | 49.18 ± 4.77 | 1.2 | 59.37 ± 5.29 |
9d | 12.11 ± 1.77 | 5.3 | 11.04 ± 1.25 | 5.8 | 12.23 ± 1.41 | 5.2 | 13.46 ± 1.21 | 4.7 | 42.56 ± 4.31 | 1.5 | 64.32 ± 5.81 |
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Islamov, I.I.; Dzhemileva, L.U.; Gaisin, I.V.; Makarov, A.A.; Dzhemilev, U.M.; D’yakonov, V.A. Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells. Int. J. Mol. Sci. 2025, 26, 5139. https://doi.org/10.3390/ijms26115139
Islamov II, Dzhemileva LU, Gaisin IV, Makarov AA, Dzhemilev UM, D’yakonov VA. Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells. International Journal of Molecular Sciences. 2025; 26(11):5139. https://doi.org/10.3390/ijms26115139
Chicago/Turabian StyleIslamov, Ilgiz I., Lilya U. Dzhemileva, Ilgam V. Gaisin, Alexey A. Makarov, Usein M. Dzhemilev, and Vladimir A. D’yakonov. 2025. "Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells" International Journal of Molecular Sciences 26, no. 11: 5139. https://doi.org/10.3390/ijms26115139
APA StyleIslamov, I. I., Dzhemileva, L. U., Gaisin, I. V., Makarov, A. A., Dzhemilev, U. M., & D’yakonov, V. A. (2025). Novel Tetraene Macrodiolides Are Effective Inducers of Mitochondrial Apoptosis in Jurkat Cells. International Journal of Molecular Sciences, 26(11), 5139. https://doi.org/10.3390/ijms26115139