Kynurenamines as neural nitric oxide synthase inhibitors.
To find new compounds with potential neuroprotective activity, we have designed, synthesized, and characterized a series of neural nitric oxide synthase (nNOS) inhibitors with a kynurenamine structure. Among them, N-[3-(2-amino-5-methoxyphenyl)-3-oxopropyl]acetamide is the main melatonin metabolite in the brain and shows the highest activity in the series, with an inhibition percentage of 65% at a 1 mM concentration. The structure-activity relationship of the new series partially reflects that of the previously reported 2-acylamido-4-(2-amino-5-methoxyphenyl)-4-oxobutyric acids, endowed with a kynurenine-like structure. Structural comparisons between these new kinurenamine derivatives, kynurenines, and 1-acyl-3-(2-amino-5-methoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives also reported confirm our previous model for the nNOS inhibition.
Entrena
Antonio
A
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, 18071 Granada, Spain.
Camacho
M Encarnación
ME
Carrión
M Dora
MD
López-Cara
Luisa C
LC
Velasco
Guillermo
G
León
Josefa
J
Escames
Germaine
G
Acuña-Castroviejo
Darío
D
Tapias
Víctor
V
Gallo
Miguel A
MA
Vivó
Antonio
A
Espinosa
Antonio
A
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D050601:Kynurenine 3-Monooxygenase / Q000037:antagonists & inhibitors; D008968:Molecular Conformation; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats
D004791:Enzyme Inhibitors; D007735:Kynuramine; C032131:N-acetyl-5-methoxy kynurenamine; D052248:Nitric Oxide Synthase Type I; D050601:Kynurenine 3-Monooxygenase