The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. General Information
4.2. Procedures for the Synthesis All the New Compounds and Their Spectroscopic Data (IR, 1H-NMR, 13C-NMR, 2D 1H-13C NMR, ESI-MS)
4.2.1. 5-Chloro-3-Methylisothiazole-4-Carbohydrazide 2
4.2.2. 5-Chloro-N’-[(1E,2E)-3-phenylprop-2-en-1-ylidene]-3-methylisothiazole-4-carbohydrazide 3
4.2.3. 5-Chloro-N’-[(E)-(3-chlorophenyl)methylidene]-3-methylisothiazole-4-carbohydrazide 4
4.2.4. 5-Chloro-N’-[(E)-(3-nitrophenyl)methylidene]-3-methylisothiazole-4-carbohydrazide 5
4.2.5. 5-Chloro-N’-[(E)-(4-ethylphenyl)methylidene]-3-methylisothiazole-4-carbohydrazide 6
4.2.6. 5-Chloro-N’-[(E)-(3-methoxyphenyl)methylidene]-3-methylisothiazole-4-carbohydrazide 7
4.2.7. 5-Chloro-N’-[(E)-phenylmethylidene]-3-methylisothiazole-4-carbohydrazide 8
4.2.8. 5-Chloro-N’-[(E)-(2,4-dimethylphenyl)methylidene]-3-methylisothiazole-4-carbohydrazide 9
4.2.9. 5-Chloro-N’-[(E)-(2-methylphenyl)methylidene]-3-methylisothiazole-4-carbohydrazide 10
4.2.10. 5-Chloro-N’-[(E)-(2-chlorophenyl)methylidene]-3-methylisothiazole-4-carbohydrazide 11
4.3. Single Crystal X-ray Structure Determination of 3, 4 and 8
4.4. Pharmacology
4.4.1. Cell Culture
4.4.2. Cells Preparing for Antiproliferative Assays
4.4.3. Cytotoxicity Assay In Vitro
MTT Assay (for MV4-11 Cell Line)
Sulforhodamine B Assay (for Other Cell Lines)
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
MV4-11 | |||||
---|---|---|---|---|---|
Name of Compound | IC50 ± SD | Name of Compound | IC50±SD | ||
[µg/mL] | μM | [µg/mL] | μΜ | ||
Cisplatin | 0.38 ± 0.14 | 1.28 ± 0.45 | 6 | 21.3 ± 8.2 | 69.4 ± 26.8 |
1 | n.a. | 7 | 22.4 ± 8.6 | 72.3 ± 27.8 | |
2 | n.a. [45%] * | 8 | 36.6 ± 11.6 | 131.2 ± 41.7 | |
3 | 4.3 ± 1.9 | 14 ± 6.4 | 9 | n.a. [42.5%] * | |
4 | 15.2 ± 2.4 | 48.4 ± 7.8 | 10 | n.a. [47%] * | |
5 | 18.7 ± 1.7 | 57.7 ± 5.3 | 11 | n.a | |
DMSO (0.5%) | 9% ** |
Name of Compound | IC50 ± SD | RI | |||||||
---|---|---|---|---|---|---|---|---|---|
MCF-7 | MCF-10A | LoVo | LoVoDX | ||||||
[µg/mL] | μM | [µg/mL] | μM | [µg/mL] | μM | [µg/mL] | μM | ||
Cisplatin | 1.56 ± 0.3 | 5.2 ± 1.0 | 2.9 ± 0.4 | 9.7 ± 1.4 | 1.7 ± 0.8 | 5.6 ± 2.6 | 0.84 ± 0.17 | 2.8 ± 0.6 | 0.49 |
3 | 12 ± 1.9 | 39.3 ± 6.3 | 20.9 ± 2.2 | 68.6 ± 7.3 | 7.64 ± 1.7 | 25 ± 5.5 | 10.4 ± 0.7 | 34.2 ± 2.3 | 1.37 |
4 | 15.2 ± 1.8 | 48.6 ± 5.7 | 24.6 ± 2.2 | 78.5 ± 7.1 | 18.6 ± 1.1 | 59.4 ± 3.4 | 15 ± 1.1 | 47.9 ± 3.7 | 0.81 |
5 | 20.1 ± 2.6 | 65.1 ± 8.4 | 60.8 ± 5.1 | 196.6 ± 16.6 | 22.7 ± 0.3 | 73.4 ± 0.8 | 29.2 ± 5.3 | 94.6 ± 17.3 | 1.29 |
6 | 13.9 ± 1.9 | 42.9 ± 5.9 | 40.6 ± 3.7 | 125.4 ± 11.3 | 31.7 ± 6.7 | 97.7 ± 20.8 | 28.8 ± 2.7 | 88.8 ± 8.4 | 0.91 |
7 | 17.8 ± 3.1 | 58 ± 10.2 | 56 ± 14.1 | 182.5 ± 48.9 | 27.8 ± 10.4 | 90.5 ± 34 | 20 ± 1.1 | 65 ± 3.5 | 0.72 |
DMSO (0.5%) | 16% ** | 5.3% ** | 10% ** | 2.7% ** | - |
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Jęśkowiak, I.; Ryng, S.; Świtalska, M.; Wietrzyk, J.; Bryndal, I.; Lis, T.; Mączyński, M. The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity. Molecules 2020, 25, 88. https://doi.org/10.3390/molecules25010088
Jęśkowiak I, Ryng S, Świtalska M, Wietrzyk J, Bryndal I, Lis T, Mączyński M. The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity. Molecules. 2020; 25(1):88. https://doi.org/10.3390/molecules25010088
Chicago/Turabian StyleJęśkowiak, Izabela, Stanisław Ryng, Marta Świtalska, Joanna Wietrzyk, Iwona Bryndal, Tadeusz Lis, and Marcin Mączyński. 2020. "The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity" Molecules 25, no. 1: 88. https://doi.org/10.3390/molecules25010088
APA StyleJęśkowiak, I., Ryng, S., Świtalska, M., Wietrzyk, J., Bryndal, I., Lis, T., & Mączyński, M. (2020). The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity. Molecules, 25(1), 88. https://doi.org/10.3390/molecules25010088