New Difunctional Derivatives of Betulin: Preparation, Characterization and Antiproliferative Potential
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Antiproliferative Activity
2.3. Cell Cycle Study
2.4. Apoptosis Determination via Annexin V Staining
2.5. Caspase-3/7 Activity Study
2.6. Similarity to Drugs
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Procedure for the Synthesis of Betulin Derivatives
3.2.1. Procedure for the Preparation of 3-Carboxyacyl-28-O-Acetylbetulins 1-3
3.2.2. Procedure for the Preparation of 3-Carboxyacylbetulins 4-6
3.2.3. Procedure for Preparation of 3,28-Diacylbetulins 4a–f, 5a–5d, 6a, and 6b
3.3. In Vitro Studies
3.3.1. Biological Materials and Assays
3.3.2. Determination of Antiproliferative Activity
3.3.3. MTT Assay
3.3.4. SRB Assay
3.3.5. Cell Cycle Analysis
3.3.6. Apoptosis Studies Using Annexin V and Propidium Iodide Staining
3.3.7. Caspase-3/7 Activity Determination
3.3.8. Statistical Analysis
3.4. In Silico Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | IC50 [µM] | |||||||
---|---|---|---|---|---|---|---|---|
MV4-11 | A549 | MCF-7 | PC-3 | HCT116 | MiaPaca-1 | Hs249T | MCF-10A | |
1 | 2.90 ± 0.26 | 4.94 ± 0.48 | 7.02 ± 2.39 | 14.04 ± 7.02 | 6.38 ± 2.87 | 23.61 ± 3.83 | 11.64 ± 1.12 | 33.18 ± 1.91 |
2 | 4.40 ± 1.63 | 4.57 ± 1.79 | 16.64 ± 7.67 | 20.07 ± 2.12 | 10.93 ± 2.94 | 28.23 ± 4.40 | 27.57 ± 0.65 | 33.94 ± 4.24 |
3 | 3.93 ± 1.54 | 5.13 ± 0.85 | 17.27 ± 6.33 | 22.40 ± 2.56 | 13.16 ± 1.02 | 34.54 ± 5.47 | 21.88 ± 4.27 | 33.51 ± 1.88 |
4 | 4.77 ± 0.44 | 3.76 ± 2.05 | 12.14 ± 3.08 | 19.15 ± 3.76 | 11.11 ± 2.56 | 22.57 ± 6.50 | 24.45 ± 8.89 | 31.46 ± 1.71 |
4a | 0.38 ± 0.14 | 7.54 ± 1.25 | 16.48 ± 1.88 | 0.86 ± 0.25 | 7.85 ± 2.35 | 7.54 ± 0.47 | 0.49 ± 0.23 | 33.13 ± 5.18 |
4b | 3.19 ± 1.29 | 4.06 ± 1.05 | 11.73 ± 2.41 | 11.58 ± 4.51 | 7.82 ± 2.86 | 24.51 ± 2.56 | 10.68 ± 1.50 | 32.63 ± 2.41 |
4c | 3.23 ± 1.38 | 7.37 ± 2.30 | 16.59 ± 2.15 | 10.14 ± 2.46 | 8.45 ± 2.15 | 22.74 ± 5.53 | 9.68 ± 1.54 | 32.57 ± 2.15 |
4d | 5.15 ± 0.47 | 6.24 ± 1.25 | 20.59 ± 5.77 | 21.68 ± 4.52 | 16.85 ± 5.61 | 34.17 ± 2.96 | 18.72 ± 9.67 | 60.38 ± 15.91 |
4e | 3.16 ± 0.88 | 59.82 ± 22.16 | 25.70 ± 4.43 | 15.21 ± 5.91 | 23.19 ± 5.91 | 67.06 ± 14.48 | 19.79 ± 5.61 | 67.95 ± 34.86 |
4f | 46.56 ± 11.78 | Neg | 130.71 ± 8.83 | 95.79 ± 27.07 | Neg | Neg | Neg | Neg |
5 | 7.81 ± 2.80 | 9.11 ± 0.87 | 29.25 ± 3.85 | 26.97 ± 3.85 | 14.71 ± 4.55 | 30.65 ± 2.63 | 30.83 ± 1.40 | 26.80 ± 2.10 |
5a | 0.600 ± 0.175 | 10.72 ± 3.0 | 19.43 ± 3.1 | 0.85 ± 0.17 | 3.64 ± 0.6 | - | - | 12.7 ± 0.5 |
5b | 4.76 ± 0.92 | 4.15 ± 0.92 | 12.29 ± 2.92 | 21.05 ± 1.54 | 9.06 ± 2.92 | 28.42 ± 3.23 | 16.13 ± 4.76 | 33.80 ± 3.38 |
5c | 10.99 ± 1.10 | 6.59 ± 1.88 | 24.96 ± 4.87 | 22.92 ± 4.71 | 9.26 ± 0.47 | 32.03 ± 6.12 | 23.24 ± 3.77 | 32.03 ± 4.87 |
5d | 2.50 ± 0.48 | 4.62 ± 1.59 | 21.05 ± 9.89 | 16.59 ± 6.54 | 12.28 ± 4.15 | 29.19 ± 1.59 | 59.66 ± 38.60 | 34.13 ± 4.94 |
6 | 6.45 ± 2.03 | 8.66 ± 1.10 | 18.97 ± 6.45 | 26.16 ± 5.71 | 20.26 ± 5.53 | 38.13 ± 3.87 | 32.06 ± 1.66 | 31.87 ± 4.24 |
6a | 2.57 ± 1.01 | 12.94 ± 0.67 | 15.97 ± 1.01 | 0.41 ± 0.08 | 20.68 ± 9.08 | 18.49 ± 9.75 | 3.53 ± 0.67 | 49.42 ± 17.82 |
6b | 3.53 ± 0.64 | 3.21 ± 0.64 | 11.40 ± 4.17 | 13.16 ± 2.57 | 9.95 ± 0.64 | 27.45 ± 2.57 | 17.50 ± 6.26 | 30.66 ± 3.69 |
A | 41.05 ± 8.46 | 27.84 ± 10.52 | 72.40 ± 6.60 | 80.65 ± 13.41 | 40.64 ± 13.61 | 126.86 ± 16.30 | 127.69 ± 14.23 | 123.98 ± 33.00 |
B | 32.75 ± 12.87 | 14.00 ± 1.13 | 43.59 ± 15.81 | 51.50 ± 9.94 | 37.72 ± 7.45 | 144.33 ± 22.13 | 58.50 ± 15.58 | 98.48 ± 0.90 |
C a | 0.021 ± 0.008 | 0.040 ± 0.012 | 0.150 ± 0.015 | 1.27 ± 0.2 | 0.118 ± 0.02 | - | - | 0.114 ± 0.013 |
Compound | SI | ||||||
---|---|---|---|---|---|---|---|
MV4-11 | A549 | MCF-7 | PC-3 | HCT116 | MiaPaca-1 | Hs249T | |
1 | 11.44 | 6.71 | 4.73 | 2.36 | 5.20 | 1.41 | 2.85 |
2 | 7.70 | 7.43 | 2.04 | 1.69 | 3.10 | 1.20 | 1.23 |
3 | 8.82 | 6.53 | 1.94 | 1.50 | 2.55 | 0.97 | 1.53 |
4 | 6.60 | 8.36 | 2.60 | 1.64 | 2.83 | 1.39 | 1.29 |
4a | 98.92 | 4.40 | 2.01 | 38.57 | 4.22 | 4.40 | 67.0 |
4b | 10.20 | 8.04 | 2.78 | 2.82 | 4.17 | 1.33 | 3.06 |
4c | 10.10 | 4.42 | 1.96 | 3.21 | 3.85 | 1.43 | 3.37 |
4d | 11.73 | 9.68 | 2.93 | 2.78 | 3.58 | 1.77 | 3.23 |
4e | 21.50 | 1.14 | 2.60 | 4.47 | 2.93 | 1.01 | 3.40 |
5 | 3.43 | 2.94 | 0.92 | 1.01 | 1.82 | 0.87 | 0.87 |
5a | 21.17 | 1.18 | 0.65 | 14.94 | 3.49 | - | - |
5b | 7.10 | 8.15 | 2.75 | 1.61 | 3.73 | 1.19 | 2.10 |
5c | 2.91 | 4.86 | 1.28 | 1.40 | 3.46 | 1.00 | 1.38 |
5d | 13.63 | 7.38 | 1.62 | 2.06 | 2.78 | 1.17 | 0.57 |
6 | 4.94 | 3.68 | 1.68 | 1.22 | 1.57 | 0.84 | 0.99 |
6a | 19.22 | 3.82 | 3.09 | 121.0 | 2.39 | 2.67 | 14.0 |
6b | 8.68 | 9.55 | 2.69 | 2.33 | 3.08 | 1.12 | 1.75 |
28-O-acetylbetulin | 3.02 | 4.45 | 1.71 | 1.54 | 3.05 | 0.98 | 0.97 |
betulin | 3.01 | 7.03 | 2.26 | 1.91 | 2.61 | 0.68 | 1.68 |
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Chrobak, E.; Świtalska, M.; Wietrzyk, J.; Bębenek, E. New Difunctional Derivatives of Betulin: Preparation, Characterization and Antiproliferative Potential. Molecules 2025, 30, 611. https://doi.org/10.3390/molecules30030611
Chrobak E, Świtalska M, Wietrzyk J, Bębenek E. New Difunctional Derivatives of Betulin: Preparation, Characterization and Antiproliferative Potential. Molecules. 2025; 30(3):611. https://doi.org/10.3390/molecules30030611
Chicago/Turabian StyleChrobak, Elwira, Marta Świtalska, Joanna Wietrzyk, and Ewa Bębenek. 2025. "New Difunctional Derivatives of Betulin: Preparation, Characterization and Antiproliferative Potential" Molecules 30, no. 3: 611. https://doi.org/10.3390/molecules30030611
APA StyleChrobak, E., Świtalska, M., Wietrzyk, J., & Bębenek, E. (2025). New Difunctional Derivatives of Betulin: Preparation, Characterization and Antiproliferative Potential. Molecules, 30(3), 611. https://doi.org/10.3390/molecules30030611