Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds
Abstract
1. Introduction
2. Results
2.1. Chemistry
2.2. In Vitro Anticancer Activity
2.3. Molecular Docking
2.4. Prediction of ADMET Properties
3. Discussion
4. Materials and Methods
4.1. General Information
4.2. Synthesis of [Et3NH][HSO4]
4.3. Synthesis of 6-Amino-4-(substituted phenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles
4.4. Evaluation of In Vitro Anticancer Activity
4.5. Molecular Docking Study
4.6. In Silico ADMET Prediction
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Not available. |
Solvent | Temperature (°C) | Time (min) | Yield (%) |
---|---|---|---|
Polyethylene glycol (PEG) | 80 | 60 | 72 |
Deep eutectic solvent of cholinechloride:urea | 80 | 20 | 92 |
Ionic liquid (N-methylpyridiniumtosylate) | 120 | 75 | 62 |
Ionic liquid (triethylammonium hydrogen sulphate[Et3NH][HSO4]) | R.T. | 15 | 94 |
[Et3NH][HSO4] mol % | Time (min) | Yield (%) |
---|---|---|
- | 60 | 00 |
5 | 50 | 50 |
10 | 45 | 65 |
15 | 15 | 70 |
20 | 15 | 94 |
25 | 15 | 85 |
Run | Time (min) | Yield (%) |
---|---|---|
1 | 15 | 94 |
2 | 15 | 82 |
3 | 15 | 78 |
4 | 15 | 75 |
Compounds | GI50 Against Cancer Cell Line in µM | Total Score -Logki | Crash Score | Polar Score | |||
---|---|---|---|---|---|---|---|
MAD-MB-231 | HeLa | SK-MEL-2 | K-562 | ||||
5b | 0.74 | >100 | <0.1 | 11.2 | 6.4039 | −0.9801 | 2.0598 |
5d | 25.76 | >100 | <0.1 | 6.41 | 5.4734 | −1.3871 | 4.449 |
5g | 2.02 | >100 | 2.92 | 40.73 | 4.6919 | −0.4209 | 5.4948 |
5h | 49.84 | >100 | 0.12 | 4.57 | 4.5247 | −0.184 | 3.7291 |
5j | 66.65 | >100 | <0.1 | 9.47 | 4.6555 | −0.7369 | 3.5549 |
ADR | <0.1 | 0.03 | <0.1 | <0.1 | NA | NA | NA |
CL2 | NA | NA | NA | NA | 5.1969 | −0.8748 | 3.5552 |
Lig_ID | %ABS (<100%) | MW (<500) | LogP (<5) | PSA (<150) | n-RotB (<10) | n-RigB (<25) | HBD (<5) | HBA (<10) | RatioH/C (<1) | Toxicity |
---|---|---|---|---|---|---|---|---|---|---|
5a | 78.64 | 252.3 | 2.64 | 87.72 | 1 | 17 | 2 | 2 | 0.357 | Non Toxic |
5b | 78.64 | 286.7 | 3.29 | 87.72 | 1 | 17 | 2 | 2 | 0.428 | Non Toxic |
5c | 78.64 | 270.3 | 2.78 | 87.72 | 1 | 17 | 2 | 2 | 0.428 | Non Toxic |
5d | 75.55 | 282.3 | 2.65 | 96.95 | 2 | 17 | 2 | 3 | 0.4 | Non Toxic |
5e | 71.76 | 268.3 | 2.34 | 108 | 1 | 17 | 3 | 3 | 0.428 | Non Toxic |
5f | 68.57 | 298.3 | 2.35 | 117.2 | 2 | 17 | 3 | 4 | 0.466 | Non Toxic |
5g | 72.37 | 312.3 | 2.65 | 106.2 | 3 | 17 | 2 | 4 | 0.437 | Non Toxic |
5h | 62.93 | 297.3 | 3.07 | 127.7 | 2 | 18 | 2 | 4 | 0.571 | Non Toxic |
5i | 78.64 | 258.3 | 2.7 | 116 | 1 | 16 | 2 | 3 | 0.5 | Non Toxic |
5j | 75.55 | 358.4 | 4.22 | 96.95 | 4 | 23 | 2 | 3 | 0.5 | Non Toxic |
CL2 | 75 | 252.3 | 2.64 | 87.72 | 1 | 17 | 2 | 2 | 0.357 | Non Toxic |
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Nimbalkar, U.D.; Seijas, J.A.; Vazquez-Tato, M.P.; Damale, M.G.; Sangshetti, J.N.; Nikalje, A.P.G. Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds. Molecules 2017, 22, 1628. https://doi.org/10.3390/molecules22101628
Nimbalkar UD, Seijas JA, Vazquez-Tato MP, Damale MG, Sangshetti JN, Nikalje APG. Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds. Molecules. 2017; 22(10):1628. https://doi.org/10.3390/molecules22101628
Chicago/Turabian StyleNimbalkar, Urja D., Julio A. Seijas, Maria Pilar Vazquez-Tato, Manoj G. Damale, Jaiprakash N. Sangshetti, and Anna Pratima G. Nikalje. 2017. "Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds" Molecules 22, no. 10: 1628. https://doi.org/10.3390/molecules22101628
APA StyleNimbalkar, U. D., Seijas, J. A., Vazquez-Tato, M. P., Damale, M. G., Sangshetti, J. N., & Nikalje, A. P. G. (2017). Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds. Molecules, 22(10), 1628. https://doi.org/10.3390/molecules22101628