Design, Synthesis, and In Vitro Activity of Pyrazine Compounds
Abstract
:1. Introduction
2. Results
2.1. Structure Retrieval and Validation
2.2. Small Molecule Docking
2.3. Synthetic Strategy
2.4. Biological Effect of Intermediates (21, 22) in Human Cancer Cell Lines
2.5. Biological Effect of Intermediate 9 and final 10 in Human Cancer Cell Lines
3. Discussion
4. Materials and Methods
4.1. Small Molecule Docking
4.2. Chemistry
4.2.1. General Information
4.2.2. Experimental Procedures and Analytical Data
4.3. Cell Culture
4.4. Cell Viability Analysis
4.5. Apoptosis Assessment
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Intermediate 9 | 24h | 48h | 72h | ||||||
---|---|---|---|---|---|---|---|---|---|
MTT | SRB | CVE | MTT | SRB | CVE | MTT | SRB | CVE | |
MCF7 | - | - | 0.1 µM (17%) | 0.001 µM (27%) | - | 0.001 µM (9%) | 0.001 µM (12%), 0.01 µM (11%), 1 µM (9%) | 0.1 µM (7%), 1 µM (10%) | |
HCT116 | 0.01 µM (18%), 0.1 µM (16%) | - | - | - | - | - | - | - | |
MOR | 0.001 µM (20%), 0.1 µM (13%) | - | - | 0.001 µM (19%), 0.01 µM (16%) | 0.01 µM (13%) | - | 0.001 µM (30%), 0.01 µM (31%) | 0.01 µM (25%) | 0.1 µM (9%) |
Intermediate 10 | 24 h | 48 h | 72 h | ||||||
---|---|---|---|---|---|---|---|---|---|
MTT | SRB | CVE | MTT | SRB | CVE | MTT | SRB | CVE | |
MCF7 | 0.001 µM (13%), 0.1 µM (20%) | - | 1 µM (10%) | - | - | 0.01 µM (6%) | - | - | 0.001 µM (8%), 0.01 µM (11%), 0.1 µM (15%), 1 µM (8%) |
MDA-MB-231 | 0.01 µM (16%), 0.1 µM (30%) | - | - | - | - | - | 0.1 µM (13%) | - | - |
HCT116 | 0.001 µM (19%), 0.01 µM (14%), 0.1 µM (32%) | - | - | - | - | - | 0.01 µM (25%), 0.1 µM (22%) | - | - |
MOR | 0.001 µM (17%), 0.01 µM (28%), 0.1 µM (27%) | - | - | 0.01 µM (31%), 0.1 µM (23%) | 1 µM (24%) | - | 0.001 µM (25%), 0.01 µM (38%), 0.1 µM (33%) | - | - |
MCF7 | Untreated (48h) | 0.001 µM (48 h) | Untreated (72h) | 1 µM (72 h) |
---|---|---|---|---|
Living Cells | 88.48% | 86.53% | 78.21% | 78.21% |
Early Apoptotic | 0.41% | 0.38% | 1.62% | 1.51% |
Late Apoptotic | 1.84% | 1.38% | 6.45% | 5.91% |
Dead Cells | 1.3% | 2.34% | 1.52% | 2.34% |
MOR | Untreated | 0.01 µM (48 h) | Untreated | 0.01 µM (72 h) | Untreated | 0.1 µM (72 h) |
---|---|---|---|---|---|---|
Living Cells | 43.11% | 42.53% | 61.21% | 64.78% | 61.21% | 61.26% |
Early Apoptotic | 9.99% | 7.75% | 4.56% | 4.59% | 4.56% | 5.63% |
Late Apoptotic | 33.85% | 29.62% | 20.64% | 12.06% | 20.64% | 15.22% |
Dead Cells | 6.05% | 13.14% | 9.23% | 13.35% | 9.23% | 12.76% |
MDA-MB-231 | Untreated | 0.1 µM (24 h) |
---|---|---|
Living Cells | 69.6% | 56.79% |
Early Apoptotic | 3.02% | 3.16% |
Late Apoptotic | 14.24% | 27.72% |
Dead Cells | 2.39% | 2.52% |
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Parsonidis, P.; Shaik, M.; Serafeim, A.P.; Vlachou, I.; Daikopoulou, V.; Papasotiriou, I. Design, Synthesis, and In Vitro Activity of Pyrazine Compounds. Molecules 2019, 24, 4389. https://doi.org/10.3390/molecules24234389
Parsonidis P, Shaik M, Serafeim AP, Vlachou I, Daikopoulou V, Papasotiriou I. Design, Synthesis, and In Vitro Activity of Pyrazine Compounds. Molecules. 2019; 24(23):4389. https://doi.org/10.3390/molecules24234389
Chicago/Turabian StyleParsonidis, Panagiotis, Mahammad Shaik, Athanasia Panagiota Serafeim, Ioanna Vlachou, Vasiliki Daikopoulou, and Ioannis Papasotiriou. 2019. "Design, Synthesis, and In Vitro Activity of Pyrazine Compounds" Molecules 24, no. 23: 4389. https://doi.org/10.3390/molecules24234389