Abstract
5-Aminosalicylic acid is one of the drugs most commonly used for inflammatory bowel disease treatment, although its use is limited due to side effects. The aim of this work was to synthesize four 5-ASA derivatives (1-4) and analyze their pharmacological effects. The compound structures were elucidated by spectral (IR and 1H and 13C-NMR) analysis, and their analgesic effects and lethal doses 50 (LD50) were evaluated in the mouse model. In addition, their Log Ps and affinities for both cyclooxygenase enzymes (COX I and COX II) were evaluated through theoretical calculations. All compounds showed analgesic activities from 0.1 mg/Kg to 16 mg/Kg in the mouse model. The imides showed more affinity by COX enzymes and their Log Ps were the highest. The docking calculations showed that all compounds have good affinities for COX I and COX II (≅ 1 μM), making π π, van der Waals interactions and hydrogen bonds. The toxicities of all compounds were low, judging by the LD50. Finally, the docking analysis show that the compounds act on COX enzymes and their analgesic effects could be mediated in part by the inhibition of these enzymes.
Keywords: 5-ASA, COX-inhibitor, docking, amides, imides
Medicinal Chemistry
Title: Synthesis and Theoretical Calculations of 5-Aminosalicylic Acid Derivatives as Potential Analgesic Agents
Volume: 4 Issue: 1
Author(s): Trujillo-Ferrara Jose, Correa-Basurto Jose, M. C. Rosales-Hernandez, Ramirez-San Juan Eduardo, Badillo Abigail, Z. Gomez-Castro Carlos and L. H. Fabila-Castillo
Affiliation:
Keywords: 5-ASA, COX-inhibitor, docking, amides, imides
Abstract: 5-Aminosalicylic acid is one of the drugs most commonly used for inflammatory bowel disease treatment, although its use is limited due to side effects. The aim of this work was to synthesize four 5-ASA derivatives (1-4) and analyze their pharmacological effects. The compound structures were elucidated by spectral (IR and 1H and 13C-NMR) analysis, and their analgesic effects and lethal doses 50 (LD50) were evaluated in the mouse model. In addition, their Log Ps and affinities for both cyclooxygenase enzymes (COX I and COX II) were evaluated through theoretical calculations. All compounds showed analgesic activities from 0.1 mg/Kg to 16 mg/Kg in the mouse model. The imides showed more affinity by COX enzymes and their Log Ps were the highest. The docking calculations showed that all compounds have good affinities for COX I and COX II (≅ 1 μM), making π π, van der Waals interactions and hydrogen bonds. The toxicities of all compounds were low, judging by the LD50. Finally, the docking analysis show that the compounds act on COX enzymes and their analgesic effects could be mediated in part by the inhibition of these enzymes.
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Jose Trujillo-Ferrara, Jose Correa-Basurto, Rosales-Hernandez C. M., Eduardo Juan Ramirez-San, Abigail Badillo, Carlos Gomez-Castro Z. and Fabila-Castillo H. L., Synthesis and Theoretical Calculations of 5-Aminosalicylic Acid Derivatives as Potential Analgesic Agents, Medicinal Chemistry 2008; 4 (1) . https://dx.doi.org/10.2174/157340608783331489
DOI https://dx.doi.org/10.2174/157340608783331489 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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