title: Synthesis and theoretical calculations of 5-aminosalicylic acid derivatives as potential analgesic agents.
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 ( identical with 1 microM), making pi-pi, 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.
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Departamento de Bioquímica, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México City, México.
authors.forename: Correa-Basurto
authors.initials: CB
authors.lastname: José
authors.forename: M C
authors.initials: MC
authors.lastname: Rosales-Hernández
authors.forename: Ramírez-San Juan
authors.initials: RS
authors.lastname: Eduardo
authors.forename: Badillo
authors.initials: B
authors.lastname: Abigail
authors.forename: Z Gómez-Castro
authors.initials: ZG
authors.lastname: Carlo
authors.forename: L H
authors.initials: LH
authors.lastname: Fabila-Castillo
authors.forename: Trujillo-Ferrara
authors.initials: TF
authors.lastname: José
mesh_terms: D000636:Aminosalicylic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000700:Analgesics / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D003198:Computer Simulation; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D007700:Kinetics; D007928:Lethal Dose 50; D008024:Ligands; D008297:Male; D051379:Mice
chemical_list: D000636:Aminosalicylic Acids; D000700:Analgesics; D016861:Cyclooxygenase Inhibitors; D008024:Ligands