Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. X-Ray Crystallography
2.3. In Vitro Cell Viability Assay
2.4. Inhibition of NF-κB Activity and Cell Signaling In Vitro
2.5. Inhibition of TNF-α Secretion
3. Materials and Methods
3.1. Chemistry
3.1.1. General Information
3.1.2. Synthesis
3.2. X-Ray Crystallography
3.3. Cell Cultivation
3.4. Cell Viability Determination
3.5. Determination of NF-κB Activity
3.6. Immunocytochemical Analysis of NF-κB Nuclear Migration
3.7. Signaling Pathway Analysis
3.8. Differentiation Monocytes into Macrophages and Evaluation of TNF-α Secretion
3.9. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Formula | C15H11BrFNO |
---|---|
Formula weight | 320.16 |
Temperature | 150(2) K |
Wavelength | 0.71073 Å |
Crystal system | Monoclinic |
Space group | P21/c |
Unit cell dimensions | a = 9.410(3) Å, α = 90° |
b = 14.645(5) Å, β = 108.633(15)° | |
c = 10.184(4) Å, γ = 90° | |
Volume | 1329.9(8) Å3 |
Z | 4 |
Density (calculated) | 1.599 g/cm3 |
Absorption coefficient | 3.093 mm−1 |
F(000) | 640 |
Crystal size | 0.140 × 0.140 × 0.060 mm |
Theta range for data collection | 2.284 to 24.999° |
Index ranges | −11 ≤ h ≤ 11, −17 ≤ k ≤ 17, −12 ≤ l ≤ 12 |
Reflections collected | 22311 |
Independent reflections | 2339 [R(int) = 0.1233] |
Absorption correction | Semi-empirical from equivalents |
Refinement method | Full-matrix least-squares on F2 |
Data/restraints/parameters | 2339/0/160 |
Goodness-of-fit on F2 | 1.067 |
Final R indices [I > 2σ(I)] | R1 = 0.0523, wR2 = 0.1295 |
R indices (all data) | R1 = 0.0746, wR2 = 0.1391 |
Largest diff. peak and hole | 1.162 and −1.065 e.Å−3 |
D-H···A | d(D-H) | d(H···A) | d(D···A) | <(DHA) |
---|---|---|---|---|
N(1)-H(1)···O(1)(i) | 0.88 | 2.20 | 3.065(5) | 167.5 |
C(2)-H(2) ···O(1)(i) | 0.95 | 2.71 | 3.507(6) | 141.8 |
Br(1)···O(1)(i) | – | – | 3.346(3) | – |
Comp. | R | IC50 [µM] ± SEM | NF-κB inhibition [%] | πAr a | MV a [cm3] |
---|---|---|---|---|---|
1 | H | >30 | 0 b | 1.76 | 80.88 |
2 | 3-CH3 | >30 | 9.00 b | 2.22 | 97.11 |
3 | 4-CH3 | >30 | 8.50 b | 2.22 | 97.11 |
4 | 2-F | >30 | 2.87 b | 2.26 | 85.90 |
5 | 3-F | >30 | 9.67 b | 1.78 | 85.90 |
6 | 3-CF3 | 11.60 ± 1.13 | 16.67 b | 2.73 | 113.57 |
7 | 2,5-CH3 | >30 | 14.78 b | 2.68 | 113.27 |
8 | 2,5-Cl | >30 | 22.50b | 2.73 | 103.54 |
9 | 2,6-Cl | >30 | 14.11 b | 2.72 | 103.54 |
10 | 3,4-Cl | 6.28 ± 2.32 | 10.89 c | 2.77 | 103.54 |
11 | 3,5-Cl | 2.43 ± 1.06 | 16.22 c | 2.90 | 103.54 |
12 | 2,6-Br | >30 | 23.12b | 2.85 | 107.33 |
13 | 3,5-CF3 | 2.17 ± 1.19 | 19.67 c | 3.98 | 145.57 |
14 | 2-F-5-Br | >30 | 19.67 b | 2.87 | 99.09 |
15 | 2-Br-5-F | >30 | 17.78 b | 2.28 | 99.09 |
16 | 2-Cl-4-Br | >30 | 13.67 b | 3.09 | 105.44 |
17 | 2-Cl-5-CF3 | >30 | 27.12b | 3.28 | 124.72 |
18 | 2-OCH3-5-NO2 | >30 | 17.56 b | 1.12 | 115.77 |
CA | – | >30 | 11.44 b | – | – |
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Hošek, J.; Kos, J.; Strhársky, T.; Černá, L.; Štarha, P.; Vančo, J.; Trávníček, Z.; Devínsky, F.; Jampílek, J. Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives. Molecules 2019, 24, 4531. https://doi.org/10.3390/molecules24244531
Hošek J, Kos J, Strhársky T, Černá L, Štarha P, Vančo J, Trávníček Z, Devínsky F, Jampílek J. Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives. Molecules. 2019; 24(24):4531. https://doi.org/10.3390/molecules24244531
Chicago/Turabian StyleHošek, Jan, Jiří Kos, Tomáš Strhársky, Lucie Černá, Pavel Štarha, Ján Vančo, Zdeněk Trávníček, Ferdinand Devínsky, and Josef Jampílek. 2019. "Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives" Molecules 24, no. 24: 4531. https://doi.org/10.3390/molecules24244531