Pharmacochemical Studies of Synthesized Coumarin–Isoxazole–Pyridine Hybrids
Abstract
:1. Introduction
2. Results and Discussion
2.1. Biology
2.2. Biochemistry
3. Materials and Methods
3.1. Materials
3.2. Chemistry
General Procedure of the 1,3-dipolar Cycloaddition Reactions of Propargyl Coumarins with Pyridine Aldoximes and Synthesis of (3-(pyridin-2-yl)isoxazol-5-yl)methoxy)-2H-chromen-2-one (3a)
- (3-(Pyridin-2-yl)isoxazol-5-yl)methoxy)-2H-chromen-2-one (3a)
- 4-Methyl-7-((3-(pyridin-4-yl)isoxazol-5-yl)methoxy)-2H-chromen-2-one (3b).
3.3. Biological Experiments
3.3.1. Inhibition of Linoleic Acid Peroxidation
3.3.2. Soybean Lipoxygenase Inhibition Study
3.4. Biochemical Experiments
3.4.1. Cell Culture
3.4.2. Cytotoxicity Evaluation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DMSO | Dimethyl Sulfoxide |
SD | Standard Deviation |
TLC | Thin Layer Chromatography |
References
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Entry | Oxime | 7-Propagyl Oxycoumarin | Method 1 | Temperature | Time | Products (% Yield) |
---|---|---|---|---|---|---|
1 | 2 | 1a | A | r.t. | 1 h | 3a (60), 4 (20) |
2 | 2 | 1a | B | 120 °C | 1 h | 3a (48), 4 (16), 5 (9) |
3 | 2 | 1a | C | Reflux | 18 h | 3a (34), 5 (32) |
4 | 2 | 1b | A | r.t. | 15 h | 3b (65), 4 (17) |
5 | 2 | 1b | B | 120 °C | 1 h | 3b (43), 4 (17), 5 (11) |
6 | 2 | 1b | C | Reflux | 18 h | 3b (44), 4 (15), 5 (13) |
7 | 6 | 1a | A 2 | r.t. | 18 h | 7a (24) |
8 | 6 | 1a | C | Reflux | 18 h | 7a (61) |
9 | 6 | 1b | A 2 | r.t. | 18 h | 7b (30) |
10 | 6 | 1b | C | Reflux | 18 h | 7b (53) |
11 | 8 | 1a | D | Reflux | 2 d | 9a (24) |
12 | 8 | 1a | C | Reflux | 18 h | 9a (42) |
13 | 8 | 1b | D | Reflux | 2 d | 9b (12) |
14 | 8 | 1b | C | Reflux | 18 h | 9b (45) |
Entry | Oxime | 4-Propargylcoumarin | Method 1 | Temperature | Time | Products (% Yield) |
---|---|---|---|---|---|---|
1 | 2 | 10a | B | 100 °C | 1 h | 11a (44), 4 (27) |
2 | 2 | 10a | C | Reflux | 18 h | 11a (62), 4 (5), 5 (11) |
3 | 2 | 10b | B | 100 °C | 2 h | 11b (55) |
4 | 6 | 10a | D | Reflux | 2 d | 12a (30) |
5 | 6 | 10a | C | Reflux | 18 h | 12a (33) |
6 | 6 | 10b | C | Reflux | 18 h | 12b (56) |
7 | 8 | 10a | D | Reflux | 2 d | 13a (55) |
8 | 8 | 10a | C | Reflux | 18 h | 13a (40) |
Entry | Compounds 1 | Clog P 2 | LOX(%)/ IC50 µM | ILP (%) |
---|---|---|---|---|
1 | 3a | 2.27 | no | 66 |
2 | 3b | 2.77 | no | 0.6 |
3 | 7a | 2.27 | 10 µM | 42 |
4 | 7b | 2.27 | no | 2 |
5 | 9a | 2.77 | 38 | 83.6 |
6 | 9b | 2.77 | no | 86.6 |
7 | 11a | 2.27 | no | 86 |
8 | 11b | 1.95 | no | 66 |
9 | 12a | 2.01 | 10 | 72 |
10 | 12b | 1.95 | 18 | 90.4 |
11 | 13a | 2.01 | 5 µM | 44.6 |
12 | NDGA | 0.45 μΜ | ||
13 | Trolox | 93 |
Entry | Compound | HeLa, EC50 (μM) | HT-29, EC50 (μM) | H1437, EC50 (μM) |
---|---|---|---|---|
1 | 7a | >100 | >100 | >100 |
2 | 9a | >100 | >100 | >100 |
3 | 12b | 38.1 ± 2.1 | 96.5 ± 6.6 | 47.3 ± 3.1 |
4 | 13a | 44.2 ± 1.9 | 65.8 ± 5.4 | 74.8 ± 4.4 |
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Douka, M.D.; Sigala, I.M.; Gabriel, C.; Nikolakaki, E.; Hadjipavlou-Litina, D.J.; Litinas, K.E. Pharmacochemical Studies of Synthesized Coumarin–Isoxazole–Pyridine Hybrids. Molecules 2025, 30, 1592. https://doi.org/10.3390/molecules30071592
Douka MD, Sigala IM, Gabriel C, Nikolakaki E, Hadjipavlou-Litina DJ, Litinas KE. Pharmacochemical Studies of Synthesized Coumarin–Isoxazole–Pyridine Hybrids. Molecules. 2025; 30(7):1592. https://doi.org/10.3390/molecules30071592
Chicago/Turabian StyleDouka, Matina D., Ioanna M. Sigala, Catherine Gabriel, Eleni Nikolakaki, Dimitra J. Hadjipavlou-Litina, and Konstantinos E. Litinas. 2025. "Pharmacochemical Studies of Synthesized Coumarin–Isoxazole–Pyridine Hybrids" Molecules 30, no. 7: 1592. https://doi.org/10.3390/molecules30071592
APA StyleDouka, M. D., Sigala, I. M., Gabriel, C., Nikolakaki, E., Hadjipavlou-Litina, D. J., & Litinas, K. E. (2025). Pharmacochemical Studies of Synthesized Coumarin–Isoxazole–Pyridine Hybrids. Molecules, 30(7), 1592. https://doi.org/10.3390/molecules30071592