Rational Design, Synthesis, Molecular Docking, and Biological Evaluations of New Phenylpiperazine Derivatives of 1,2-Benzothiazine as Potential Anticancer Agents
Abstract
:1. Introduction
Rational Design of New Compounds
2. Results and Discussion
2.1. Chemistry
2.2. In Vitro Antiproliferative Activity
2.2.1. Effect of New Compounds on MCF10A and MCF7 Cell Viability
2.2.2. Effect of New Compounds in Combination with Doxorubicin on MCF10A and MCF7 Cell Viability
Effect of New Compounds in Combination with Doxorubicin on MCF10A Cell Viability
Effect of New Compounds in Combination with Doxorubicin on MCF7 Cell Viability
2.2.3. Structure–Activity Relationship (SAR) Analysis
SAR Analysis in the Study of the Effect of New Compounds on MCF10A and MCF7 Cell Viability
SAR Analysis in the Study of the Effect of New Compounds in Combination with Doxorubicin on MCF10A and MCF7 Cells Viability
2.2.4. Therapeutic Potential of the Tested Compounds
- Decreased viability of MCF7 cells while maintaining toxicity similar to DOX towards MCF10A cells;
- Decreased toxicity towards MCF10A cells while maintaining toxicity similar to DOX towards MCF7 cells;
- Decreased viability of MCF7 cells while simultaneously reducing toxicity towards MCF10A cells.
2.3. Fluorescence Spectroscopic Study of Binding to DNA
2.4. Molecular Docking Studies
3. Summary
4. Materials and Methods
4.1. Chemistry
- General procedure for the preparation of series A and series B compounds
- Synthesis and properties of series A compounds
- Synthesis and properties of series B compounds
4.2. Biological Experiments
4.2.1. Cell Lines
4.2.2. Cell Culture
4.2.3. Preparation of Compounds for In Vitro Testing
4.2.4. Cell Viability Testing
4.2.5. Statistical Analysis
4.3. Fluorescence Studies
4.4. Molecular Docking Studies
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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Compound | Ksv (1 × 103) (M−1) | kq (1 × 1011) (M−1 s−1) | K (1 × 103) (M−1) | n | R2 |
---|---|---|---|---|---|
BS62 | 2.16 | 2.16 | 2.34 | 0.92 | 0.995 |
BS130 | 3.32 | 3.32 | 3.21 | 0.99 | 0.997 |
BS133 | 1.35 | 1.35 | 0.61 | 1.02 | 0.994 |
BS230 | 2.41 | 2.41 | 2.86 | 1.01 | 0.996 |
BS233 | 1.98 | 1.98 | 2.13 | 0.97 | 0.997 |
BS433 | 3.23 | 3.23 | 2.64 | 0.99 | 0.995 |
BS533 | 3.06 | 3.06 | 3.96 | 0.99 | 0.995 |
BS633 | 3.41 | 3.41 | 3.12 | 1.01 | 0.998 |
Compound | ∆Gbinding to DNA [kJ/mol] | ∆Gbinding to Topo IIα [kJ/mol] |
---|---|---|
BS62 | −61.1 | −63.2 |
BS130 | −61.3 | −63.2 |
BS133 | −57.1 | −63.1 |
BS230 | −63.2 | −66.6 |
BS233 | −60.2 | −64.2 |
BS433 | −62.2 | −65.6 |
BS533 | −58.7 | −64.1 |
BS633 | −58.4 | −63.0 |
etoposide | −48.3 | −44.6 |
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Szczęśniak-Sięga, B.M.; Zaręba, N.; Czyżnikowska, Ż.; Janek, T.; Kepinska, M. Rational Design, Synthesis, Molecular Docking, and Biological Evaluations of New Phenylpiperazine Derivatives of 1,2-Benzothiazine as Potential Anticancer Agents. Molecules 2024, 29, 4282. https://doi.org/10.3390/molecules29184282
Szczęśniak-Sięga BM, Zaręba N, Czyżnikowska Ż, Janek T, Kepinska M. Rational Design, Synthesis, Molecular Docking, and Biological Evaluations of New Phenylpiperazine Derivatives of 1,2-Benzothiazine as Potential Anticancer Agents. Molecules. 2024; 29(18):4282. https://doi.org/10.3390/molecules29184282
Chicago/Turabian StyleSzczęśniak-Sięga, Berenika M., Natalia Zaręba, Żaneta Czyżnikowska, Tomasz Janek, and Marta Kepinska. 2024. "Rational Design, Synthesis, Molecular Docking, and Biological Evaluations of New Phenylpiperazine Derivatives of 1,2-Benzothiazine as Potential Anticancer Agents" Molecules 29, no. 18: 4282. https://doi.org/10.3390/molecules29184282