Synthesis and theoretical calculations of 5-Aminosalicylic acid derivatives as potential analgesic agents

José Correa-Basurto, M. C. Rosales-Hernández, Eduardo Ramírez-San Juan, Abigail Badillo, Z. Gómez-Castro Carlos, L. H. Fabila-Castillo, José Trujillo-Ferrara

Research output: Contribution to journalArticle

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 and1H and13C-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. © 2008 Bentham Science Publishers Ltd.
Original languageAmerican English
Pages (from-to)25-29
Number of pages22
JournalMedicinal Chemistry
DOIs
StatePublished - 1 Jan 2008

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