Design, Synthesis and Study of Nitrogen Monoxide Donors as Potent Hypolipidaemic and Anti-Inflammatory Agents
Abstract
1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Hypolipidaemic Effect
2.3. Nitrogen Monoxide Release
2.4. Lipoxygenase Inhibitory Activity
2.5. Antioxidant and Radical Scavenging Activity
2.6. In Vivo Anti-Inflammatory Activity
3. Materials and Methods
3.1. General
3.2. Synthesis
3.2.1. 2-Nitrooxy-Ethanol [9]
3.2.2. General Procedures for the Synthesis of Compounds 1–9
3.3. Biological Evaluation
3.3.1. Effect on Plasma Cholesterol, Triglyceride and LDL-Cholesterol Levels
3.3.2. In Vitro NO Release
3.3.3. In Vitro Evaluation of Lipoxygenase Activity
3.3.4. In Vitro Lipid Peroxidation
3.3.5. In Vitro Interaction with the Stable Radical 1,1-Diphenyl-2-Picrylhydrazyl (DPPH)
3.3.6. Carrageenan-Induced Paw Oedema
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Compound | Dose (i.p.) (μmol/kg) | % Reduction | ||
---|---|---|---|---|
TC a | TG b | LDL-C c | ||
1 | 150 | 62.2 ** | 30.1 ** | 80.0 * |
3 | 150 | 71.7 ** | 31.8 ** | 62.3 * |
4 | 150 | 78.2 *** | 38.9 *** | 84.6 *** |
5 | 150 | 46.6 ** | 40.2 *** | 57.8 *** |
6 | 150 | 70.9 *** | 54.4 *** | 74.8 *** |
7 | 150 | 65.5 ** | 45.7 *** | 60.6 * |
9 | 150 | 55.4 *** | 30.0 *** | 65.0 *** |
Simvastatin | 150 | 73.0 *** | - | 70.0 *** |
Ibuprofen | 300 | 41.0 *** | 38.0 *** | 41.6 *** |
Naproxen | 500 | 53.0 *** | 43.5 *** | 25.5 *** |
Compound | ΝΟ Release (μΜ)/Compound | ||||||
---|---|---|---|---|---|---|---|
1 | 3 | 4 | 5 | 6 | 7 | 9 | |
500 μM | 116 | 102 | 73 | 100 | 98 | 77 | 93 |
250 μM | 82 | 58 | 37 | 57 | 51 | 38 | 49 |
125 μM | 40 | 28 | 17 | 26 | 22 | 17 | 23 |
62.5 μM | 17 | 13 | 7 | 11 | 11 | 6.5 | 10 |
31.25 μM | 7 | 5 | 2.5 | 4 | 5 | 2 | 3 |
Compound | IC50 (μM) | clogP |
---|---|---|
1 | 46 | 4.65 |
2 | 24 | 5.92 |
3 | 107 | 5.15 |
4 | >>300 | 3.78 |
5 | 86 | 3.73 |
6 | 220 | 3.18 |
7 | 44 | 6.16 |
8 | 10.5 | 7.44 |
9 | 120 | 4.16 |
Ibuprofen | 200 | |
Ketoprofen | 220 | |
Trolox | >>300 | 3.10 |
NDGA | 1.3 |
Compound | Percent Interaction with DPPH | Inhibition of Lipid Peroxidation IC50 (μΜ) | ||
---|---|---|---|---|
200 μΜ | 100 μΜ | 50 μΜ | ||
7 | 87 | 49 | 21 | 41 |
8 | 88 | 57 | 23 | 150 |
9 | 92 | 90 | 55 | 2.3 |
Trolox | 92 | 90 | 38 | 25 |
Compound | % Oedema Reduction |
---|---|
1 | 76 ** |
2 | 53 * |
3 | 29 ** |
4 | 70 ** |
5 | 75 ** |
6 | 61 ** |
7 | 55 ** |
8 | 51 ** |
9 | 57 ** |
Ibuprofen | 36 * |
Indomethacin | 42 * |
Naproxen | 11 * |
Ketoprofen | 47 * |
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Theodosis-Nobelos, P.; Papagiouvanis, G.; Pantelidou, M.; Kourounakis, P.N.; Athanasekou, C.; Rekka, E.A. Design, Synthesis and Study of Nitrogen Monoxide Donors as Potent Hypolipidaemic and Anti-Inflammatory Agents. Molecules 2020, 25, 19. https://doi.org/10.3390/molecules25010019
Theodosis-Nobelos P, Papagiouvanis G, Pantelidou M, Kourounakis PN, Athanasekou C, Rekka EA. Design, Synthesis and Study of Nitrogen Monoxide Donors as Potent Hypolipidaemic and Anti-Inflammatory Agents. Molecules. 2020; 25(1):19. https://doi.org/10.3390/molecules25010019
Chicago/Turabian StyleTheodosis-Nobelos, Panagiotis, Georgios Papagiouvanis, Maria Pantelidou, Panos N. Kourounakis, Chrysoula Athanasekou, and Eleni A. Rekka. 2020. "Design, Synthesis and Study of Nitrogen Monoxide Donors as Potent Hypolipidaemic and Anti-Inflammatory Agents" Molecules 25, no. 1: 19. https://doi.org/10.3390/molecules25010019
APA StyleTheodosis-Nobelos, P., Papagiouvanis, G., Pantelidou, M., Kourounakis, P. N., Athanasekou, C., & Rekka, E. A. (2020). Design, Synthesis and Study of Nitrogen Monoxide Donors as Potent Hypolipidaemic and Anti-Inflammatory Agents. Molecules, 25(1), 19. https://doi.org/10.3390/molecules25010019