Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Anti-Inflammatory/Analgesic Activities and Ulcerogenicity Studies
2.3. Docking Studies
3. Experimental Section
3.1. General Procedures
3.2. Preparation
3.2.1. General Procedures for the Preparation of Ester (5a–e) and Hydrazide (6a–e) Derivatives
3.2.2. General Procedures for the Preparation of N-Acyl Hydrazone Derivatives (4a–e)
3.3. Pharmacology
3.3.1. Anti-Inflammatory Activity
3.3.2. Analgesic Activity
3.3.3. Ulcerogenicity Studies
3.4. Docking Studies
4. Conclusions
Acknowledgments
Conflicts of Interest
- Author ContributionsThais Regina Ferreira de Melo and Rafael Consolin Chelucci participated in synthesis, anti-inflammatory and analgesic assays, Maria Elisa Lopes Pires participate in gastroulceration studies, Luiz Antônio Dutra participated in synthesis, purification and characterization of the compounds 4a–e, Karina Pereira Barbieri participated in analgesic study, Gustavo Henrique Trossini participated in molecular modeling studies, Priscila Longhin Bosquesi, Man Chin Chung and Jean Leandro dos Santos participated in the interpretation of the results and in manuscript writing.
References
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Compounds | N | % Inhibition mean ± S.E.M. | |||||
---|---|---|---|---|---|---|---|
60 min | 120 min | 180 min | 240 min | 300 min | 360 min | ||
Indomethacin | 6 | 66.7 ± 1.3 | 71.8 ± 0.96 | 75.7 ± 1.32 | 78.8 ± 2.13 | 76.6 ± 1.93 | 75.7 ± 0.98 |
Diclofenac | 6 | 59.3 ± 0.27 * | 64.7 ± 1.21 * | 66.6 ± 1.48 * | 69.2 ± 1.71 * | 68.2 ± 0.98 * | 75.1 ± 2.11 * |
4a | 6 | 0 † | 0 † | 0 † | 0 † | 0 † | 0 † |
Salicylic acid | 6 | 63.4 ± 2.31 * | 58.9 ± 1.83 * | 73.3 ± 2.44 * | 73.0 ± 1.17 * | 72.7 ± 1.76 * | 74.1 ± 2.10 * |
4b | 6 | 7.6 ± 0.10 † | 14.9 ± 0.08 † | 11.3 ± 0.07 † | 12.5 ± 0.09 † | 12.2 ± 0.08 † | 32.1 ± 0.05 † |
Naproxen | 6 | 65.8 ± 1.32 * | 72.7 ± 1.32 * | 69.2 ± 1.61 * | 58.8 ± 0.91 | 53.9 ± 1.77 | 41.9 ± 1.87 |
4c | 6 | 8.0 ± 0.10 † | 35.9 ± 0.11 † | 35.0 ± 0.11 † | 52.8 ± 0.07 † | 67.5 ± 0.04 †,* | 81.5 ± 0.04 * |
Ibuprofen | 6 | 64.8 ± 1.86 * | 42.1 ± 2.18 * | 46.7 ± 1.73 * | 42.3 ± 1.6 * | 45.5 ± 1.55 * | 62.5 ± 2.09 * |
4d | 6 | 22.7 ± 0.07 † | 25.7 ± 0.05 † | 9.7 ± 0.09 † | 10.6 ± 0.08 † | 22.9 ± 0.08 † | 45 ± 0.07 † |
Ketoprofen | 6 | 71.8 ± 1.68 * | 64.7 ± 1.54 * | 63.8 ± 2.21 * | 66.9 ± 1.72 * | 72.7 ± 1.31 * | 75.1 ± 1.84 * |
4e | 6 | 11.3 ± 0.08 † | 15.7 ± 0.04 † | 16.1 ± 0.05 † | 18.5 ± 0.07 † | 29.4 ± 0.1 † | 34.7 ± 0.12 † |
Compounds | % Protection |
---|---|
Dypirone | 37.2 ± 1.4 |
Diclofenac | 28.3 ± 2.2 |
4a | 42.0 ± 1.1 †,* |
Salicylic acid | 30.2 ± 1.5 |
4b | 36.8 ± 2.1 * |
Naproxen | 36.8 ± 0.8 |
4c | 36.4 ± 1.7 |
Ibuprofen | 25.0 ± 0.7 |
4d | 28.1 ± 1.0 † |
Ketoprofen | 22.3 ± 0.9 |
4e | 25.6 ± 2.2 † |
Compounds | Number of ulcers | <1 mm | 1–2 mm | >2 mm |
---|---|---|---|---|
Celecoxib | 11 ± 3.1 | 7.5 ± 2.7 (68.2%) | 3.5 ± 1.4 (31.8%) | - |
Diclofenac | 72 ± 6.9 | 60 ± 7.7 (83.3%) | 8.1 ± 5.3 (11.3%) | 3.9 ± 3.1 (5.4%) |
4a | 26 ± 7.7 †,* | 20.8 ± 4.8 (80%) | 5.2 ± 2.1 (20%) | - |
Salicylic acid | 69.8 ± 3.4 | 52.56 ± 5.2 (75.2%) | 9.21 ± 3.6 (13.2%) | 8.03 ± 2.7 (11.6%) |
4b | 17.5 ± 3.3 * | 14.3 ± 3.9 (81.7%) | 3.2 ± 1.1 (18.3%) | - |
Naproxen | 57.8 ± 4.2 | 47.97 ± 2.7 (83%) | 9.82 ± 0.8 (17%) | - |
4c | 7.1 ± 2.8 * | 6.5 ± 2.8 (91.5%) | 0.6 ± 0.2 (8.5%) | - |
Ibuprofen | 70.7 ± 4.4 | 52.31 ± 6.1 (73.9) | 16.54 ± 2.8 (23.4%) | 1.83 ± 0.8 (2.7%) |
4d | 14.1 ± 3.5 * | 13 ± 3.6 (92.2%) | 1.1 ± 1.2 (7.8%) | - |
Ketoprofen | 68.9 ± 3.3 | 59.46 (86.3%) | 8.33 ± 1.7 (12.1%) | 1.10 ± 0.4 (1.6%) |
4e | 8.2 ± 2.2 * | 7.4 ± 2.9 (90.2%) | 0.8 ± 0.4 (9.8%) | - |
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Share and Cite
De Melo, T.R.F.; Chelucci, R.C.; Pires, M.E.L.; Dutra, L.A.; Barbieri, K.P.; Bosquesi, P.L.; Trossini, G.H.G.; Chung, M.C.; Dos Santos, J.L. Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit. Int. J. Mol. Sci. 2014, 15, 5821-5837. https://doi.org/10.3390/ijms15045821
De Melo TRF, Chelucci RC, Pires MEL, Dutra LA, Barbieri KP, Bosquesi PL, Trossini GHG, Chung MC, Dos Santos JL. Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit. International Journal of Molecular Sciences. 2014; 15(4):5821-5837. https://doi.org/10.3390/ijms15045821
Chicago/Turabian StyleDe Melo, Thais Regina Ferreira, Rafael Consolin Chelucci, Maria Elisa Lopes Pires, Luiz Antonio Dutra, Karina Pereira Barbieri, Priscila Longhin Bosquesi, Gustavo Henrique Goulart Trossini, Man Chin Chung, and Jean Leandro Dos Santos. 2014. "Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit" International Journal of Molecular Sciences 15, no. 4: 5821-5837. https://doi.org/10.3390/ijms15045821