Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast
Abstract
:1. Introduction
2. Results and Discussion
2.1. Drug-Likeness and Bioactivity Scores
2.2. Cell Multiplication Study after 4a–c Compounds Treatment
2.3. Cell Cycle Analysis
2.4. Actin Cytoskeleton
3. Materials and Methods
3.1. In Silico Study
3.2. Synthesis
3.3. Cell Culture and Culturing Conditions
3.4. Cell Treatment
3.5. Evaluation of Cell Multiplication and Cell Cycle Studies by Flow Cytometry
3.6. Actin Cytoskeleton Staining
3.7. Statistics
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | Mol. wt 1 | H-Bond Donors 2 | H-Bond Acceptors 3 | C Log P 4 | TPSA (Å2) 5 |
---|---|---|---|---|---|
Rule | ≤500 | ≤5 | ≤10 | ≤5 | ≤140 |
4a | 484.64 | 2 | 3 | 6.88 | 41.14 |
4b | 484.64 | 2 | 3 | 6.88 | 41.12 |
4c | 502.68 | 2 | 3 | 5.96 | 41.12 |
Cisplatin | 300,05 | 6 | 2 | −4.58 | 55.28 |
Compound | Caco2 1 Permeability | HIA 2 (%) | PPB 3 (%) | BBB 4 (Cbrain/Cblood) |
---|---|---|---|---|
Rule | ≥4 | ≥70 | ≥90 | ≥0.4 |
4a | 48.3202 | 95.542381 | 97.857647 | 8.62779 |
4b | 48.3128 | 95.542356 | 97.212995 | 8.82546 |
4c | 23.9496 | 96.734547 | 100.000000 | 0.992983 |
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Knyazev, N.A.; Shmakov, S.V.; Pechkovskaya, S.A.; Filatov, A.S.; Stepakov, A.V.; Boitsov, V.M.; Filatova, N.A. Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast. Int. J. Mol. Sci. 2021, 22, 8264. https://doi.org/10.3390/ijms22158264
Knyazev NA, Shmakov SV, Pechkovskaya SA, Filatov AS, Stepakov AV, Boitsov VM, Filatova NA. Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast. International Journal of Molecular Sciences. 2021; 22(15):8264. https://doi.org/10.3390/ijms22158264
Chicago/Turabian StyleKnyazev, Nickolay A., Stanislav V. Shmakov, Sofya A. Pechkovskaya, Alexander S. Filatov, Alexander V. Stepakov, Vitali M. Boitsov, and Natalia A. Filatova. 2021. "Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast" International Journal of Molecular Sciences 22, no. 15: 8264. https://doi.org/10.3390/ijms22158264