Synthesis of Novel 2-(Cyclopentylamino)thiazol-4(5H)-one Derivatives with Potential Anticancer, Antioxidant, and 11β-HSD Inhibitory Activities
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Inhibitory Activity towards 11β-HSD
2.2.1. In Vitro Studies
2.2.2. Molecular Docking
2.3. Anticancer Activity
2.4. Antioxidant Activity
3. Materials and Methods
3.1. General Information
3.2. Reagents and Solvents
3.3. General Procedures of Synthesis
3.3.1. Procedure A (Synthesis of Compounds 3a-3c)
3.3.2. Procedure B (Synthesis of Compounds 3d-3e)
3.3.3. Procedure C (Synthesis of Compounds 3f-3i)
3.4. Inhibition of 11β-HSD Assays
3.4.1. 11β-HSD1
3.4.2. 11β-HSD2
3.4.3. Determination of IC50
3.5. Molecular Docking
3.6. Cell Culture
3.7. Metabolic Activity
3.8. Antioxidant Activity
3.9. Statistical Analysis
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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No. | R1 | R2 | Procedure | Isolated Yield [%] | M.p. (°C) |
---|---|---|---|---|---|
3a | H | CH3 | A | 5.39 * | 127.1–128.9 |
3b | H | C2H5 | A | 69.29 * | 132.1–134.0 |
3c | H | C3H7 | A | 81.63 * | 112.4–114.0 |
3d | H | CH(CH3)2 | B | 19.88 | 135.0–138.0 |
3e | CH3 | CH3 | B | 9.42 | 179.0–181.0 |
3f | H | C6H5 | C | 71.06 | 183.0–184.0 |
3g | H | C6H4p-Br | C | 85.48 | 220 (dec.) |
3h | -(CH2)5- | C | 2.47 | 207.7–209.1 | |
3i | -(CH2)3- | C | 27.86 | 202.4–203.1 |
No. | R1 | R2 | % of 11β-HSD1 Inhibition 10 μM | IC50 11β-HSD1 [µM] | % of 11β-HSD2 Inhibition 10 μM |
---|---|---|---|---|---|
3a | H | CH3 | 10.94 ± 4.08 | >10 | 40.27 ± 0.65 |
3b | H | C2H5 | 21.33 ± 3.29 | >10 | 39.70 ± 0.07 |
3c | H | C3H7 | 56.58 ± 6.11 | 2.75 ± 0.12 | 37.70 ± 6.07 |
3d | H | CH(CH3)2 | 82.93 ± 2.62 | 0.46 ± 0.07 | 38.57 ± 3.69 |
3e | CH3 | CH3 | 53.17 ± 5.22 | 4.40 ± 0.15 | 36.61 ± 1.50 |
3f | H | C6H5 | 64.29 ± 5.07 | 1.10 ± 0.08 | 36.55 ± 3.07 |
3g | H | C6H4p-Br | 86.96 ± 2.17 | 0.18 ± 0.03 | 38.60 ± 1.39 |
3h | -(CH2)5- | 90.49 ± 1.31 | 0.07 ± 0.005 | 42.82 ± 0.96 | |
3i | -(CH2)3- | 71.25 ± 4.77 | 1.55 ± 0.10 | 46.33 ± 1.22 | |
Control | 90.42 ± 1.86 a | 0.08 ± 0.006 a | 55.22 ± 0.13 a 46.82 ± 3.75 b |
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Baumgart, S.; Kupczyk, D.; Archała, A.; Koszła, O.; Sołek, P.; Płaziński, W.; Płazińska, A.; Studzińska, R. Synthesis of Novel 2-(Cyclopentylamino)thiazol-4(5H)-one Derivatives with Potential Anticancer, Antioxidant, and 11β-HSD Inhibitory Activities. Int. J. Mol. Sci. 2023, 24, 7252. https://doi.org/10.3390/ijms24087252
Baumgart S, Kupczyk D, Archała A, Koszła O, Sołek P, Płaziński W, Płazińska A, Studzińska R. Synthesis of Novel 2-(Cyclopentylamino)thiazol-4(5H)-one Derivatives with Potential Anticancer, Antioxidant, and 11β-HSD Inhibitory Activities. International Journal of Molecular Sciences. 2023; 24(8):7252. https://doi.org/10.3390/ijms24087252
Chicago/Turabian StyleBaumgart, Szymon, Daria Kupczyk, Aneta Archała, Oliwia Koszła, Przemysław Sołek, Wojciech Płaziński, Anita Płazińska, and Renata Studzińska. 2023. "Synthesis of Novel 2-(Cyclopentylamino)thiazol-4(5H)-one Derivatives with Potential Anticancer, Antioxidant, and 11β-HSD Inhibitory Activities" International Journal of Molecular Sciences 24, no. 8: 7252. https://doi.org/10.3390/ijms24087252