Methyl Derivatives of Flavone as Potential Anti-Inflammatory Compounds
Abstract
1. Introduction
2. Results
2.1. The Cytotoxic Effect of 2′-Methylflavone (5C), 3′-Methylflavone (6C), 4′-Methylflavone (7C), 6-Methylflavone (8C), and 6-Methyl-8-nitroflavone (12C) on RAW 264.7 Macrophages
2.2. The Nitric Oxide Production by LPS-Stimulated RAW 264.7 Cells in the Presence of Flavone and Its Methyl Derivatives: 2′-Methylflavone (5C), 3′-Methylflavone (6C), 4′-Methylflavone (7C), 6-Methylflavone (8C), and 6-Methyl-8-nitroflavone (12C)
2.3. The Effect of Flavone and Its Methyl Derivatives, 2′-Methylflavone (5C), 3′-Methylflavone (6C), 4′-Methylflavone (7C), 6-Methylflavone (8C), and 6-Methyl-8-nitroflavone (12C), on Chemiluminescence of Activated RAW 264.7 Macrophages
2.4. The Effect of Flavone and Its Methyl Derivatives, 2′-Methylflavone (5C), 3′-Methylflavone (6C), 4′-Methylflavone (7C), 6-Methylflavone (8C), and 6-Methyl-8-nitroflavone (12C), on the Release of IL-1α, IL-1β, IL-6, IL-12p70 and TNF-α by RAW 264.7 Macrophages
3. Discussion
4. Materials and Methods
4.1. Synthesis of Methyl Derivatives of Flavone
- 2′-Methylflavone (5C). ESI/MS m/z 237.1 ([M + H]+, C16H12O2); 1H NMR (600 MHz, acetone-d6) δ (ppm): 8.15 (1H, dd, J = 7.9, 1.7, H-5), 7.82 (1H, ddd, J = 8.7, 7.2, 1.7, H-7), 7.64 (2H, m, H-8 and H-6′), 7.50 (2H, m, H-6 and H-4′), 7.40 (2H, m, H-3′ and H-5′), 6.42 (1H, s, H-3), 2.51 (3H, s, C-2′-CH3); 13C NMR (151 MHz, acetone-d6) δ (ppm): 177.8 (C-4), 166.7 (C-2), 157.4 (C-8a), 134.9 (C-7), 137.7 (C-2′), 133.7 (C-1′), 132.1 (C-3′), 131.6 (C-4′), 130.2 (C-6′), 127.1 (C-5′), 126.2 (C-6), 126.0 (C-5), 124.7 (C-4a), 119.2 (C-8), 112.4 (C-3), 20.5 (C-2′-CH3).
- 3′-Methylflavone (6C). ESI/MS m/z 237.1 ([M + H]+, C16H12O2); 1H NMR (600 MHz, acetone-d6) δ (ppm): 8.12 (1H, dd, J = 7.9, 1.6, H-5), 7.92 (1H, s, H-2′), 7.88 (1H, d, J = 7.7, H-6′), 7.81 (1H, ddd, J = 8.6, 7.1, 1.7, H-7), 7.73 (1H, dd, J = 8.4, 0.9, H-8), 7.48 (2H, m, H-5′ and H-6), 7.42 (1H, d, J = 7.5, H-4′), 6.85 (1H, s, H-3), 2.45 (3H, s, C-3′-CH3); 13C NMR (151 MHz, acetone-d6) δ (ppm): 177.7 (C-4), 164.9 (C-2), 157.1 (C-8a), 139.8 (C-3′), 134.8 (C-7), 133.2 (C-4′), 132.7 (C-1′), 129.9 (C-5′), 127.7 (C-2′), 126.1 (C-6), 126.0 (C-5), 124.9 (C-4a), 124.4 (C-6′), 119.2 (C-8), 107.9 (C-3), 21.4 (C-2′-CH3).
- 4′-Methylflavone (7C). ESI/MS m/z 237.1 ([M + H]+, C16H12O2); 1H NMR (600 MHz, acetone-d6) δ (ppm): 8.12 (1H, dd, J = 7.9, 1.6, H-5), 7.99 (2H, d, J = 8.3, H-2′ and 6′), 7.81 (1H, ddd, J = 8.7, 7.1, 1.7, H-7), 7.73 (1H, d, J = 8.4, H-8), 7.48 (1H, m, H-6), 7.41 (2H, d, J = 8.0, H-3′ and H-5′), 6.82 (1H, s, H-3), 2.43 (3H, s, C-3′-CH3); 13C NMR (151 MHz, acetone-d6) δ (ppm): 177.9 (C-4), 164.1 (C-2), 157.2 (C-8a), 143.1 (C-4′), 134.7 (C-7), 130.6 (C-3′ and C-5′), 127.2 (C-2′ and C-6′), 126.1 (C-6), 126.0 (C-5), 124.9 (C-4a), 123.0 (C-1′), 119.2 (C-8), 107.4 (C-3), 21.4 (C-2′-CH3).
- 6-Methylflavone (8C). ESI/MS m/z 237.1 ([M + H]+, C16H12O2); 1H NMR (600 MHz, acetone-d6) δ (ppm): 8.12 (2H, m, H-2′ and H-6′), 7.94 (1H, s, H-5), 7.67 (2H, s, H-7 and H-8); 7.63 (3H, m, H-3′, H-4′, H-5′); 6.88 (1H, s, H-3); 2.50 (3H, s, C6-CH3); 13C NMR (151 MHz, acetone-d6) δ (ppm):178.0 (C-4), 163.8 (C-2), 155.4 (C-8a), 136.1 (C-6), 135.9 (C-8), 132.8 (C-1′), 132.4 (C-4′), 130.0 (C-3′ and C-5′), 127.2 (C-2′ and C-6′), 125.3 (C-5), 124.5 (C-4a), 119.0 (C-7), 107.8 (C-3), 20.9 (C6-CH3).
- 6-Methyl-8-nitroflavone (12C). ESI/MS m/z 282.1 ([M + H]+, C16H11NO4; 1H NMR (600 MHz; acetone-d6) δ (ppm): 8.35 (1H, dd, J = 2.2, 0.5 Hz, H-7), 8.24 (1H, dd, J = 2.2, 0.8 Hz, H-5), 8.15 (2H, ddd, J = 5.7, 4.3, 2.5 Hz, H-2′, H-6′), 7.65–7.61 (3H, m, H-3′, H-4′, H-5′), 7.01 (1H, s, H-3), 2.59 (3H, s, C-6-CH3); 13C NMR (151 MHz, acetone-d6) δ (ppm): 176.23 (C-4), 163.90 (C-2), 147.56 (C-8a), 139.61 (C-8), 136.24 (C-6), 133.00 (C-4′), 131.92 (C-1′), 131.57 (C-5), 131.53 (C-7), 130.11, (C-3′, C-5′), 127.45 (C-2′, C-6′), 126.31 (C-4a), 107.97 (C-3), 20.60 (C-6-CH3).
4.2. Cell Culture
4.3. Cell Viability Assay
4.4. Nitric Oxide Release Assay
4.5. Chemiluminescence Detection
4.6. Bio-Plex Multiplex Immunoassay
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Structure | R1 | R2 | R3 | R4 | R5 |
---|---|---|---|---|---|---|
5C | H | H | CH3 | H | H | |
6C | H | H | H | CH3 | H | |
7C | H | H | H | H | CH3 | |
8C | CH3 | H | H | H | H | |
12C | CH3 | NO2 | H | H | H |
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Jaworska, D.; Kłósek, M.; Bronikowska, J.; Krawczyk-Łebek, A.; Perz, M.; Kostrzewa-Susłow, E.; Czuba, Z.P. Methyl Derivatives of Flavone as Potential Anti-Inflammatory Compounds. Int. J. Mol. Sci. 2025, 26, 729. https://doi.org/10.3390/ijms26020729
Jaworska D, Kłósek M, Bronikowska J, Krawczyk-Łebek A, Perz M, Kostrzewa-Susłow E, Czuba ZP. Methyl Derivatives of Flavone as Potential Anti-Inflammatory Compounds. International Journal of Molecular Sciences. 2025; 26(2):729. https://doi.org/10.3390/ijms26020729
Chicago/Turabian StyleJaworska, Dagmara, Małgorzata Kłósek, Joanna Bronikowska, Agnieszka Krawczyk-Łebek, Martyna Perz, Edyta Kostrzewa-Susłow, and Zenon P. Czuba. 2025. "Methyl Derivatives of Flavone as Potential Anti-Inflammatory Compounds" International Journal of Molecular Sciences 26, no. 2: 729. https://doi.org/10.3390/ijms26020729
APA StyleJaworska, D., Kłósek, M., Bronikowska, J., Krawczyk-Łebek, A., Perz, M., Kostrzewa-Susłow, E., & Czuba, Z. P. (2025). Methyl Derivatives of Flavone as Potential Anti-Inflammatory Compounds. International Journal of Molecular Sciences, 26(2), 729. https://doi.org/10.3390/ijms26020729