TY - JOUR
T1 - Synthesis and theoretical calculations of 5-Aminosalicylic acid derivatives as potential analgesic agents
AU - Correa-Basurto, José
AU - Rosales-Hernández, M. C.
AU - Ramírez-San Juan, Eduardo
AU - Badillo, Abigail
AU - Gómez-Castro Carlos, Z.
AU - Fabila-Castillo, L. H.
AU - Trujillo-Ferrara, José
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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.
AB - 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.
KW - 5-ASA
KW - Amides
KW - COX-inhibitor
KW - Docking
KW - Imides
UR - http://www.scopus.com/inward/record.url?scp=40049100192&partnerID=8YFLogxK
U2 - 10.2174/157340608783331489
DO - 10.2174/157340608783331489
M3 - Artículo
SN - 1573-4064
VL - 4
SP - 25
EP - 29
JO - Medicinal Chemistry
JF - Medicinal Chemistry
IS - 1
ER -