Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors
Abstract
:1. Introduction
2. Results and Discussion
2.1. Design and Synthesis
2.2. In Vitro COX-1, COX-2 and 5-LOX Inhibition Assay
2.3. Evaluation of Redox Activity of Synthesized Compounds
3. Materials and Methods
3.1. General
3.2. Synthesis of Compounds 1–13
3.2.1. Synthesis of Compounds 1–3
3.2.2. Synthesis of Compounds 4–7
3.2.3. Synthesis of Compounds 8 and 9
3.2.4. Synthesis of Compound 10
3.2.5. Synthesis of Compounds 11–12
3.2.6. Synthesis of Compound 13
3.3. In Vitro COX-1, COX-2 and 5-LOX Inhibition Assay
3.3.1. COX-1 and COX-2 Inhibition
3.3.2. 5-LOX Inhibition
3.4. Evaluation of Antioxidant Activity of Synthesized Compounds
3.4.1. Sample Collection
3.4.2. Biochemical Parameters
3.4.3. Statistics
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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Compound | COX-2 IC50 (µM) | 5-LOX IC50 (µM) | COX-1 IC50 (µM) |
---|---|---|---|
1 | 18.28 ± 2.17 | 5.71 ± 0.15 | >100 |
2 | 6.72 ± 0.79 | 1.62 ± 0.67 | >100 |
3 | 5.26 ± 0.34 | 1.73 ± 0.64 | >100 |
4 | >100 | 8.10 ± 2.12 | Not tested |
5 | 10.64 ± 0.80 | 9.30 ± 1.87 | >100 |
6 | 6.89 ± 0.83 | 53.84 ± 11.87 | >100 |
7 | >100 | 12.55 ± 3.36 | Not tested |
8 | >100 | 14.52 ± 3.62 | Not tested |
9 | >100 | >100 | Not tested |
10 | >100 | 13.01 ± 2.67 | Not tested |
11 | 36.18 ± 3.08 | 1.04 ± 0.22 | >100 |
12 | 83.42 ± 4.37 | 1.29 ± 0.10 | >100 |
13 | >100 | 13.58 ± 3.54 | Not tested |
Celecoxib | 0.07 ± 0.01 | Not tested | Not tested |
Zileuton | Not tested | 0.36 ± 0.10 | Not tested |
2 h Incubation | 24 h Incubation | |||||
---|---|---|---|---|---|---|
TBH added | p | TBH added | p | |||
1 | −0.43 (−1.27–3.13) | 6.44 (5.51–7.02) | 0.023 | 0.71 (0.51–0.80) | 5.46 (4.96–6.20) | <0.001 |
2 | 3.28 (−0.68–16.66) | 5.20 (3.70–5.42) | 0.597 | 0.33 (−0.07–0.85) | 6.79 (4.37–7.90) | <0.001 |
3 | 1.58 (−0.38–3.45) | 5.81 (4.64–7.25) | 0.023 | 1.31 (−0.31–1.75) | 1.93 (0.65–5.02) # | 0.226 |
4 | 0.24 (−0.24–0.89) | 3.68 (3.36–8.40) | 0.001 | 3.00 (1.99–3.93) ** | 7.86 (7.20–10.68) | 0.016 |
5 | 0.29 (−0.30–1.23) | 2.83 (2.55–3.39) | <0.001 | 2.14 (1.37–2.62) ** | 5.64 (5.07–6.47) | <0.001 |
6 | 0.52 (0.08–1.52) | 3.77 (3.37–4.20) | 0.002 | 3.09 (2.50–3.67) | 6.07 (4.34–7.02) | 0.016 |
7 | 3.12 (2.21–3.47) | 6.62 (6.42–6.98) | 0.021 | 2.55 (2.18–2.92) | 10.54 (4.45–27.42) | 0.021 |
8 | 0.03 (−0.96–1.46) | 8.43 (5.76–13.81) | 0.010 | −0.52 (−1.24–3.03) | −0.55 (−0.67–1.48) ## | 0.762 |
9 | 0.09 (−0.79–1.80) | 5.97 (4.06–8.25) | 0.003 | −0.18 (−1.55–2.91) | −0.19 (−0.68–1.56) | 0.450 |
10 | −0.64 (−0.84−0.30) | 6.34 (5.07–22.02) | <0.001 | −0.97 (−1.53–3.85) | 0.97 (−0.04–4.08) | 0.199 |
11 | −0.22 (−0.65–0.82) | 5.15 (4.76–6.74) | <0.001 | 1.83 (1.49–2.18) * | 3.18 (2.92–3.60) ## | <0.001 |
12 | 0.24 (−0.06–0.58) | 4.79 (4.25–5.43) | <0.001 | 2.49 (2.03–2.66) ** | 3.97 (3.44–6.33) | <0.001 |
13 | 0.75 (0.56–0.94) | 5.89 (5.63–6.14) | <0.001 | 0.64 (0.19–1.01) | 2.35 (2.10–3.92) # | <0.001 |
BHT | 3.08 (2.73–3.26) | 7.98 (6.77–8.81) | 0.021 | 2.62 (2.14–3.22) | 4.51 (4.38–7.22) | 0.021 |
Celecoxib | 5.66 (2.92–12.90) | 7.94 (6.97–8.45) | 0.564 | 2.77 (2.46–3.27) | 4.95 (4.57–10.25) | 0.021 |
Zileuton | 2.60 (−7.86–7.54) | 6.87 (6.52–7.18) | 0.248 | 3.61 (2.47–4.93) | 8.80 (5.71–13.66) | 0.043 |
Urea | 3.48 (3.44–4.08) | 8.11 (7.61–8.79) | 0.021 | 4.60 (3.62–6.02) | 5.19 (4.96–14.00) | 0.149 |
Trolox | 0.54 (−0.66–2.43) | / | / | 0.07 (−0.59–0.59) * | / | / |
TBH | 6.40 (4.66–11.59) | / | / | 6.43 (4.73–12.00) | / | / |
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Bošković, J.; Dobričić, V.; Mihajlović, M.; Kotur-Stevuljević, J.; Čudina, O. Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. Pharmaceuticals 2023, 16, 549. https://doi.org/10.3390/ph16040549
Bošković J, Dobričić V, Mihajlović M, Kotur-Stevuljević J, Čudina O. Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. Pharmaceuticals. 2023; 16(4):549. https://doi.org/10.3390/ph16040549
Chicago/Turabian StyleBošković, Jelena, Vladimir Dobričić, Marija Mihajlović, Jelena Kotur-Stevuljević, and Olivera Čudina. 2023. "Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors" Pharmaceuticals 16, no. 4: 549. https://doi.org/10.3390/ph16040549