Phosphodiesterase Inhibition and Immunotropic Activity of Dipyridamole Dynamic Derivatives
Abstract
:1. Introduction
2. Materials and Methods
2.1. Planning (Methodology) of Research
2.2. Molecular Dynamics
2.3. Synthesis of (IV)
2.4. Detection of Derivative (IV) Effect on Activity of PDE
2.5. Animals, Diarrhea, and Immunodeficiency
- Control (intact);
- Mice with diarrhea caused by STM;
- Mice with diarrhea caused by STM and immunosuppression caused by CFA;
- Mice with diarrhea caused by STM and treated by D3;
- Mice with diarrhea caused by STM and immunosuppression caused by CFA and treated by D3;
- Mice with diarrhea caused by STM and treated by D10;
- Mice with diarrhea caused by STM and immunosuppression caused by CFA and treated by D10.
Immunological Methods
2.6. Preparation of Peritoneal Macrophages
2.7. Preparation of Splenic T Lymphocytes
2.8. IL-2 Assay
2.9. Statistical Analysis
3. Results
3.1. Molecular Dynamics
3.2. Synthesis and Analysis of Dynamic Dipyridamole
3.3. Study of the Derivative’s Phosphodiesterase Inhibition Ability
Item No. | Reagent Molecular Ratio * | IC50 **1, µM | ||
---|---|---|---|---|
m | k1 | k2 | ||
1 | 18 | 100 *** | 100 *** | >800 |
2 | -//- | 50 | 50 | 160 |
3 (D3) | -//- | 25 | 25 | 0.05 |
4 | -//- | 15 | 15 | 40 |
5 | -//- | 7 | 7 | 40 |
6 | -//- | 3 | 3 | 20 |
7 | -//- | 1 | 1 | 20 |
8 | -//- | 0.5 | 0.5 | 10 |
9 | -//- | 0.25 | 0.25 | 10 |
10 (D10) | - | 0 | 0 | 5 |
11 | Control from Kit 3-isobutyl-1-methylxanthine (IBMX) | 5 |
3.4. In Vivo Results
3.5. The Effect of D3 and D10 (See Table 2) on Mice Immunity
4. Discussion
5. 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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Used Substances | Day of Experiment | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | |
Streptomycin | + | + | + | + | + | + * | + * | + * | + * | * | * | * |
Cyclophosphamide | + ** | ** | ** | ** | ** | ** | ** | ** | ** | ** | ** | ** |
D3 and D10 | + | + | + | + | + | + | + |
Mice Group (n = 12) | Body Weight (g) | |
---|---|---|
Before Experiment | On the 12th Day | |
1 | 20.80 ± 0.52 | 23.12 ± 0.58 * |
2 | 22.00 ± 0.28 | 18.60 ±0.45 * |
3 | 20.88 ± 0.40 | 18.34 ± 0.66 * |
4 | 20.82 ± 0.56 | 22.88 ± 0.82 * |
5 | 20.70 ± 0.56 | 21.10 ± 0.50 |
6 | 20.65 ± 0.40 | 21.85 ± 0.40 * |
7 | 20.78 ± 0.88 | 22.65 ± 0.28 |
Mice Group ** (n = 12) | Cells, Tissue, Lymphokines | ||||||
---|---|---|---|---|---|---|---|
Il-2 Production (ng/mL) | Macrophages (TNF-a) (pg/mL) | T Cells (TNF-b) (pg/mL) | NO Production in Mouse Macrophages, µg/mL | Macrophages Number (in Millions) | Splenocytes Number (in Millions) | ||
Splenic T-Lymphocytes | Blood Plasma | ||||||
1 control | 73.92 ± 2.39 | 161.75 ± 5.15 | 15.33 ± 3.03 | 12.75 ± 2.01 | 9.92 ± 2.39 | 1.92 ± 0.67 | 127.00 ± 10.01 |
2 control | 53.75 ± 4.73 | 107.42 ± 5.74 | 8.58 ± 1.98 | 10.83 ± 3.56 | 17.17 ± 3.74 | 1.33 ± 0.49 | 107.92 ± 10.67 |
3 control | 11.75 ± 4.39 | 31.33 ± 4.31 | 2.58 ± 1.0 | 8.25 ± 1.14 | 6.33 ± 1.97 | 1.08 ± 0.29 | 89.00 ± 8.30 |
4 | 65.25 ± 5.29 | 155.50 ± 4.64 | 10.92 ± 1.98 | 10.17 ± 4.00 * | 12.25 ± 2.01 | 1.83 ± 0.94 * | 116.33 ± 5.25 |
5 | 86.33 ±5.18 | 160.00 ± 12.45 * | 18.17 ± 1.34 | 14.25 ± 3.22 * | 13.08 ± 2.23 | 1.42 ± 0.51 * | 137.50 ± 10.88 |
6 | 51.33 ± 4.79 * | 100.92 ± 8.13 | 7.25 ± 2.26 * | 7.92 ± 2.11 | 10.08 ± 3.12 | 1.50 ± 0.52 * | 105.50 ± 5.89 * |
7 | 36.50 ± 4.34 | 79.25 ± 5.64 | 2.92 ± 1.44 * | 4.17 ± 1.47 | 6.00 ± 1.41 * | 1.25 ± 0.45 * | 79.67 ± 8.40 |
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Martynov, A.; Farber, B.; Katz, A. Phosphodiesterase Inhibition and Immunotropic Activity of Dipyridamole Dynamic Derivatives. Curr. Issues Mol. Biol. 2025, 47, 214. https://doi.org/10.3390/cimb47040214
Martynov A, Farber B, Katz A. Phosphodiesterase Inhibition and Immunotropic Activity of Dipyridamole Dynamic Derivatives. Current Issues in Molecular Biology. 2025; 47(4):214. https://doi.org/10.3390/cimb47040214
Chicago/Turabian StyleMartynov, Artur, Boris Farber, and Alexander Katz. 2025. "Phosphodiesterase Inhibition and Immunotropic Activity of Dipyridamole Dynamic Derivatives" Current Issues in Molecular Biology 47, no. 4: 214. https://doi.org/10.3390/cimb47040214
APA StyleMartynov, A., Farber, B., & Katz, A. (2025). Phosphodiesterase Inhibition and Immunotropic Activity of Dipyridamole Dynamic Derivatives. Current Issues in Molecular Biology, 47(4), 214. https://doi.org/10.3390/cimb47040214