Elucidating the Structure-Activity Relationships of the Vasorelaxation and Antioxidation Properties of Thionicotinic Acid Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Tested compounds
2.2. Vasorelaxant activity
2.2.1. Effect of thionicotinic acid derivatives 6-8 on the vascular function of rat thoracic aorta in the presence and absence of L-NAME.
Thionicotinic acid 6
Thionicotinamide analog 7
Thionicotinonitrile analog 8
2.2.2. Effect of endothelial cells on vasorelaxant activity of thionicotinic acid derivatives 6-8
2.2.3. Effect of derivatives 6-8 on the vascular function of rat thoracic aorta in the presence of cyclo-oxygenase inhibitor (INDO)
2.3. Antioxidative activity
2.4. Molecular modeling of vasorelaxant and antioxidative activities
3. Conclusions
4. Experimental
4.1. General
4.2. Tested compounds 6-8
4.3. Vasorelaxant assay
4.3.1. Isometric tension measurements
4.3.2. Statistical analyses
4.4. Antioxidative assay
4.5. Molecular modeling analysis
Acknowledgments
References
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Sample Availability: Contact the authors. |
Compound | Vasorelaxant activity | ||||
---|---|---|---|---|---|
Without L-NAME | With L-NAME (1mM) | ||||
Rmax (%) | ED50 (M) | Rmax (%) | ED50 (M) | ||
6a | 78.67 ± 0.48 | 2.13 × 10-8 | 47.60 ± 0.83 | 2.50 × 10-8 | |
ACha | 108.17 ± 1.22 | 4.72 × 10-7 | 81.59 ± 0.63 | 4.92 × 10-7 | |
7b | 77.69 ± 0.47 | 1.25 × 10-7 | 43.72 ± 0.70 | 2.66 × 10-7 | |
AChb | 109.86 ± 0.65 | 5.29 × 10-7 | 83.54 ± 0.91 | 5.49 × 10-7 | |
8a | 71.64 ± 0.55 | 2.44 × 10-7 | 42.36 ± 0.98 | 3.05 × 10-7 | |
ACha | 108.17 ± 1.22 | 4.72 × 10-7 | 81.59 ± 0.27 | 4.92 × 10-7 |
Compound | Vasorelaxant activity | ||||
---|---|---|---|---|---|
+et a | −et b | ||||
Rmax (%) | ED50 (M) | Rmax (%) | ED50 (M) | ||
6c | 78.18 ± 0.79 | 6.64 × 10-8 | 0 | − | |
AChc | 104.89 ± 1.33 | 2.66 × 10-7 | 7.11 ± 0.35 | 3.13 × 10-7 | |
7d | 75.19 ± 0.59 | 1.05 × 10-7 | 0 | − | |
AChd | 103.45 ± 1.12 | 3.35 × 10-7 | 7.47 ± 0.15 | 3.13 × 10-7 | |
8d | 71.92 ± 0.52 | 3.82 × 10-7 | 0 | − | |
AChd | 103.45 ± 1.12 | 3.35 × 10-7 | 7.47 ± 0.15 | 3.13 × 10-7 |
Compound | Vasorelaxant activity | |||||||
---|---|---|---|---|---|---|---|---|
−Inhibitora | +L-NAME (1mM) | +INDO (1mM) | +L-NAME (1mM) +INDO (1mM) | |||||
Rmax (%) | ED50 (M) | Rmax (%) | ED50 (M) | Rmax (%) | ED50 (M) | Rmax (%) | ED50 (M) | |
AChb | 121.7 ± 1.44 | 9.99 × 10-7 | 81.34 ± 0.77 | 5.44 × 10-7 | 68.78 ± 0.92 | 4.58 × 10-7 | 0 | − |
6b | 77.67±0.66 | 1.78 × 10-8 | 47.44 ± 0.44 | 3.55 × 10-8 | 46.05 ± 0.26 | 7.17 × 10-8 | 0 | − |
7b | 76.93±0.56 | 1.23 × 10-7 | 43.22 ± 0.66 | 3.88 × 10-7 | 36.49 ± 0.60 | 6.34 × 10-7 | 0 | − |
8b | 71.47±0.42 | 2.05 × 10-7 | 42.10 ± 0.65 | 3.43 × 10-7 | 37.63 ± 0.62 | 6.14 × 10-7 | 0 | − |
SNPc | 120.81±1.18 | 3.16 × 10-7 | 116.70 ± 1.30 | 3.17 × 10-7 | 112.93 ± 0.61 | 3.16 × 10-7 | 104.98±1.41 | 3.17×10-7 |
Compound | % DPPH radical scavenging activitya | % NBT inhibitionb |
---|---|---|
6 | 33.20 | 15.40 |
7 | 0.57 | 15.45 |
8 | 0.30 | 17.31 |
Compound | Dipole moment (Debye) | IP (eV) | HOMO-LUMO gap (eV) | ED50 (M) |
---|---|---|---|---|
6 | 2.4098 | 0.2184 | 0.1605 | 2.13×10-8 |
7 | 3.6920 | 0.2265 | 0.1837 | 1.25×10-7 |
8 | 4.8092 | 0.2285 | 0.1669 | 2.44×10-7 |
ACh | 13.1100 | 0.3976 | 0.2800 | 4.72×10-7 |
Correlation with ED50 | 0.9594 | 0.9038 | 0.8879 |
Compound | Dipole moment (Debye) | IP (eV) | HOMO-LUMO gap (eV) | DPPH (%) | NBT (%) |
---|---|---|---|---|---|
6 | 2.4098 | 0.2184 | 0.1605 | 33.20 | 15.40 |
7 | 3.6920 | 0.2265 | 0.1837 | 0.57 | 15.45 |
8 | 4.8092 | 0.2285 | 0.1669 | 0.30 | 17.31 |
Correlation with DPPH | -0.8885 | -0.9826 | -0.7086 | ||
Correlation with NBT | 0.8575 | 0.6748 | -0.2276 |
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Prachayasittikul, S.; Wongsawatkul, O.; Worachartcheewan, A.; Nantasenamat, C.; Ruchirawat, S.; Prachayasittikul, V. Elucidating the Structure-Activity Relationships of the Vasorelaxation and Antioxidation Properties of Thionicotinic Acid Derivatives. Molecules 2010, 15, 198-214. https://doi.org/10.3390/molecules15010198
Prachayasittikul S, Wongsawatkul O, Worachartcheewan A, Nantasenamat C, Ruchirawat S, Prachayasittikul V. Elucidating the Structure-Activity Relationships of the Vasorelaxation and Antioxidation Properties of Thionicotinic Acid Derivatives. Molecules. 2010; 15(1):198-214. https://doi.org/10.3390/molecules15010198
Chicago/Turabian StylePrachayasittikul, Supaluk, Orapin Wongsawatkul, Apilak Worachartcheewan, Chanin Nantasenamat, Somsak Ruchirawat, and Virapong Prachayasittikul. 2010. "Elucidating the Structure-Activity Relationships of the Vasorelaxation and Antioxidation Properties of Thionicotinic Acid Derivatives" Molecules 15, no. 1: 198-214. https://doi.org/10.3390/molecules15010198
APA StylePrachayasittikul, S., Wongsawatkul, O., Worachartcheewan, A., Nantasenamat, C., Ruchirawat, S., & Prachayasittikul, V. (2010). Elucidating the Structure-Activity Relationships of the Vasorelaxation and Antioxidation Properties of Thionicotinic Acid Derivatives. Molecules, 15(1), 198-214. https://doi.org/10.3390/molecules15010198