RESUMO
We have designed and synthesized a series of novel molecules having a residue of a classical NSAID and an antioxidant moiety, both attached through amide bonds to a known nootropic structure, an L-proline, trans-4-hydroxy-L-proline or DL-pipecolinic acid residue. The compounds were found to retain anti-inflammatory and antioxidant activities, to acquire hypocholesterolemic action, and to possess a greatly reduced gastrointestinal toxicity. The novel molecules could find useful applications, among others, in slowing the progression or delaying the onset of neurodegenerative diseases.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Artrite/tratamento farmacológico , Inflamação/tratamento farmacológico , Ácidos Pipecólicos/farmacologia , Prolina/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anticolesterolemiantes/síntese química , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Colesterol/sangue , Modelos Animais de Doenças , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Ácidos Pipecólicos/síntese química , Ácidos Pipecólicos/química , Prolina/análogos & derivados , Prolina/síntese química , Ratos , Ratos Endogâmicos F344 , Relação Estrutura-Atividade , Triglicerídeos/sangueRESUMO
The synthesis and pharmacological evaluation of a series of amide derivatives of NSAIDs with L-cysteine ethyl ester is described. The novel derivatives are potent antiinflammatory, antioxidant and hypocholesterolemic-hypolipidemic agents, while they demonstrate considerably reduced gastrointestinal toxicity. This molecular modification may offer a general route to safer antiinflammatory agents, potentially suitable for chronic use in conditions such as neurodegenerative disorders.
