Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. General
2.2. Synthesis
Hydrazone Synthesis
2.3. Cell Culture Studies
2.3.1. 2D Anticancer Activity
2.3.2. Cell Viability
2.3.3. 3D Spheroid Formation/Growth Assay
2.4. Enzyme Inhibition Assay
2.5. Molecular Docking Study
3. Results and Discussion
3.1. Chemistry
3.2. 2D Anticancer Activity
3.3. Anticancer Activity in 3D Cell Cultures (Spheroids)
3.4. Enzyme Inhibition Results
3.5. Molecular Docking Study
3.5.1. Molecular Docking into COX-2
3.5.2. Molecular Docking into 5-LOX
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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Tested Compound | IC50 (µM) |
---|---|
7a | 7.51 ± 0.08 |
7b | 9.09 ± 1.11 |
7c | 42.77 ± 3.59 |
7d | 9.09 ± 1.04 |
7e | >100 µM |
7f | 4.86 ± 0.19 |
7g | 24.23 ± 3.76 |
7h | >100 µM |
7i | >100 µM |
7j | 9.65 ± 0.22 |
DOX | 0.35 ± 0.18 |
Tested Compound | IC50 (µM) |
---|---|
7a | 0.88 ± 0.06 |
7d | >100 µM |
7f | 0.67 ± 0.13 |
DOX | 0.11 ± 0.08 |
Sample Concentrations | Spheroid Diameter (Square Millimeters) | ||
---|---|---|---|
Day 0 | Day 9 | ||
Control | - | 1111.8 ± 95.5 | 7240.2 ± 37.1 |
DOX | 10 µM | 1194.0 ± 63.3 | 910.0 ± 29.3 |
7a | |||
0.1 µM | 1156.5 ± 14.2 | 5050.5 ± 36.9 | |
1 µM | 1186.5 ± 91.9 | 1755.0 ± 58.9 | |
10 µM | 1176.0 ± 31.1 | 636.0 ± 12.7 | |
100 µM | 1183.0 ± 36.1 | 432.0 ± 17.4 | |
7b | |||
0.1 µM | 1193.0 ± 13.1 | 5922.5 ± 39.8 | |
1 µM | 1185.5 ± 82.7 | 6461.5 ± 59.6 | |
10 µM | 969.3 ± 28.9 | 4192.0 ± 44.8 | |
100 µM | 644.7 ± 26.9 | 1050.5 ± 18.9 | |
7c | |||
0.1 µM | 1118.0 ± 31.1 | 5415.0 ± 12.7 | |
1 µM | 1168.0 ± 52.7 | 6174.0 ± 106.1 | |
10 µM | 989.5 ± 54.1 | 3729.5 ± 12.8 | |
100 µM | 940.5 ± 33.9 | 2207.0 ± 47.1 | |
7d | |||
0.1 µM | 1127.5 ± 36.1 | 4911.0 ± 117.4 | |
1 µM | 1211.0 ± 17.9 | 6312.5 ± 24.8 | |
10 µM | 1297.5 ± 55.1 | 1708.0 ± 87.1 | |
100 µM | 974.0 ± 32.2 | 445.7 ± 64.1 | |
7e | |||
0.1 µM | 1181.5 ± 33.2 | 5607.5 ± 44.55 | |
1 µM | 1153.0 ± 73.5 | 6396.0 ± 16.1 | |
10 µM | - | - | |
100 µM | - | - | |
7f | |||
0.1 µM | 1110.0 ± 113.1 | 5823.0 ± 39.8 | |
1 µM | 1108.0 ± 17.6 | 4336.0 ± 48.1 | |
10 µM | 1215.0 ± 12.7 | 2806.0 ± 31.5 | |
100 µM | - | - | |
7g | |||
0.1 µM | 1222.5 ± 28.73 | 5969.0 ± 59.6 | |
1 µM | 985.5 ± 65.7 | 3318.0 ± 35.4 | |
10 µM | - | - | |
100 µM | - | - | |
7h | |||
0.1 µM | 1125.5 ± 28.9 | 5215 ± 18.3 | |
1 µM | 1220.5 ± 31.5 | 6682.5 ± 7.1 | |
10 µM | 1192.0 ± 24.7 | 8165.5 ±18.1 | |
100 µM | 942.0 ± 58.9 | 7936.5 ± 48.6 | |
7i | |||
0.1 µM | 1135.5 ± 2.5 | 5523.0 ± 15.2 | |
1 µM | 943.0 ± 12.1 | 3539.0 ± 25.4 | |
10 µM | 118.6 ± 24.7 | 2764.0 ± 37.9 | |
100 µM | 1023.0 ± 59.5 | 2776.5 ± 85.2 | |
7j | |||
0.1 µM | 1112.0 ± 35.4 | 6291.5 ± 45.87 | |
1 µM | 998.0 ± 11.5 | 5934.0 ± 96.3 | |
10 µM | 1068.0 ± 68.1 | 5217.4 ± 25.7 | |
100 µM | - | - |
Compound | COX-2 IC50 (µM) | COX-2 Percent of İnhibition | COX-1 IC50 (µM) | 5-LOX IC50 (µM) | 5-LOX Percent of İnhibition |
---|---|---|---|---|---|
7a | - | 13.57 ± 0.38 | Not tested | 3.78 ± 0.39 | 64.38 ± 0.46 |
7b | - | 24.13 ± 1.55 | Not tested | 93.23 ± 9.89 | 25.77 ± 2.54 |
7c | 10.13 ± 0.25 | 51.97 ± 2.51 | ˃100 | 2.60 ± 0.11 | 55.05 ± 1.37 |
7d | - | 16.74 ± 3.36 | Not tested | - | 15.61 ± 0.66 |
7e | 13.86 ± 0.76 | 49.41±1.12 | ˃100 | 3.30 ± 0.07 | 60.69 ± 0.54 |
7f | 39.05 ± 3.41 | 38.41 ± 0.85 | ˃100 | 2.94 ± 0.20 | 60.56 ± 2.49 |
7g | - | 11.41 ± 3.40 | Not tested | - | 20.38 ± 1.98 |
7h | - | 8.35 ± 0.93 | Not tested | - | 19.87 ± 1.62 |
7i | - | 13.27 ± 0.73 | Not tested | - | 27.23 ± 0.64 |
7j | - | 16.64 ± 1.11 | Not tested | - | 36.10 ± 3.92 |
Celecoxib | 0.07 ± 0.01 | 85.02 ± 0.31 | ˃100 | Not tested | Not tested |
Zileuton | Not tested | Not tested | Not tested | 0.36 ± 0.10 | 64.85 ± 0.39 |
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Coskun, G.P.; Ozhan, Y.; Dobričić, V.; Bošković, J.; Reis, R.; Sipahi, H.; Sahin, Z.; Demirayak, S. Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer. Pharmaceutics 2023, 15, 1441. https://doi.org/10.3390/pharmaceutics15051441
Coskun GP, Ozhan Y, Dobričić V, Bošković J, Reis R, Sipahi H, Sahin Z, Demirayak S. Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer. Pharmaceutics. 2023; 15(5):1441. https://doi.org/10.3390/pharmaceutics15051441
Chicago/Turabian StyleCoskun, Goknil Pelin, Yagmur Ozhan, Vladimir Dobričić, Jelena Bošković, Rengin Reis, Hande Sipahi, Zafer Sahin, and Seref Demirayak. 2023. "Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer" Pharmaceutics 15, no. 5: 1441. https://doi.org/10.3390/pharmaceutics15051441
APA StyleCoskun, G. P., Ozhan, Y., Dobričić, V., Bošković, J., Reis, R., Sipahi, H., Sahin, Z., & Demirayak, S. (2023). Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer. Pharmaceutics, 15(5), 1441. https://doi.org/10.3390/pharmaceutics15051441